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Basic Science Material for Use in Modern Education 

samuel ralph powers, Administrative Officer 

Authors of the Series 

Edna W. Bailey 

Professor of Education, University of California 

George L. Bush 

Teacher of Science 
East Technical High School, Cleveland, Ohio 

F. L. Fitzpatrick 

Professor of Natural Sciences 
Teachers College, Columbia University 

C. C. Furnas 

Associate Professor of Chemical Engineering 
Yale University 

Bentley Glass 

Associate Professor of Biology 
Goucher College 

Anita D. Laton 

Assistant Professor of Health and Hygiene 
San Jose State College, San Jose, California 

Paul B. Sears 
Professor of Botany, Oberlin College 

Robert Stollberg 

Lieutenant (jg), United States Naval Reserve 


Genes and the Man 

by Bentley Glass 

Associate Professor of Biology 
Goucher College 

Bureau of Publications 

Teachers College, Columbia University 

New York, 1 943 









Editor's Foreword 

As the fifth volume in this series of basic science materials, 
Genes and the Man attempts to integrate the fields of repro- 
duction, genetics, and growth and development as they relate 
to human life. To understand an individual, whether animal 
or plant, we need to know how the hereditary pattern is 
formed at reproduction and how it reacts with environmental 
factors as growth and development of an organism take place. 
The course of development presents features which we can 
interpret only in the light of our racial past or in terms of the 
individual^ future needs. Therefore, the material here has 
been selected for its contribution toward building a concep- 

\jt tion of the individual as an organism continuously growing 

and developing along lines laid down by the hereditary pat- 

>\ tern but modifiable by external circumstances. 

Even though life begins with a hereditary pattern, we mast 
realize that the interaction of this pattern with its environment 
determines the growth and development of the individual. 
On education devolves the guidance of development after the 
uniform environment of our prenatal days is replaced by a 
constantly changing and widely diverse one. Genes alone do 
not make the man. 

The author of this volume, Bentley Glass, is a successful 
teacher of biology and a fruit-fly geneticist. As a teacher he 
is at the same time a student of human relationships and has 
endeavored to apply the theory and the findings of his research 






to the much broader and more difficult field of human genetics. 
The timeliness of its content because of its bearing upon 
current discussions of cultural conflict in relation to the 
hereditary nature of man makes the book of interest to lay- 
men as well as educators. However, it is designed primarily 
to increase the effectiveness with which educators serve society 
through the young people placed in their charge. 

Samuel Ralph Powers 


There are several textbooks on genetics, and it has not been 
my intention to add to their number. Rather, I have hoped 
to fill a gap of another kind. It appears to me important that 
we should conceive of human life in genetic terms, that we 
should understand the epic sweep of an individual's growth 
and development up to maturity and the long years of slow 
decline thereafter, together with those tenuous physical bonds 
that link each generation with all before and after— that we 
should understand these, I repeat— by tracing them from their 
beginnings in protoplasm and the genes. Physiologists, deal- 
ing with perfected structures and functions, and geneticists, 
occupied with the behavior of chromosomes, have both been 
somewhat isolated from the embryologists. No doubt, this 
condition has existed because of the highly specialized train- 
ing necessary for a scientist to do fruitful work. Yet life is a 
whole. The genes and the chromosomes are important to us 
only because of the effects they produce during the course 
of growth and development; and the completed man is fully 
intelligible only as we perceive what has made him as he is. 
It is a startling fact that this theme, which surely ought to 
form the core of our teaching of general biology, is com- 
monly relegated to the rarefied zone inhabited solely by the 
specialist student of zoology. 

Throughout the realm of science the narrow, rigid bound- 
aries of specialized fields of subject matter are at last break- 


ing down. The boundary between genetics and cytology has 
already disappeared, and it is now evident that embryology 
and physiology are beginning to enter the amalgam. As yet, 
however, this trend is apparent only in the more technical 
studies. In general education, compartmentalized biology con- 
tinues to gain ground. For these reasons this volume has been 
prepared to indicate a new outlook, not to present genetics, 
or cytology, or embryology, or physiology, or even a summary 
of all of them, but rather to describe the operation and inter- 
action of those factors which make the physical man, insofar 
as we know them or can reason about them today. 

This purpose may explain some features of the book that 
at first sight appear strange, such as the gaps in the treatment 
of his field that will strike the geneticist. Because the central 
theme is that of man's growth and development, plants are 
introduced only casually to indicate the universality of such 
phenomena as cell division and meiosis. 

To some extent, the relative proportions of the sections of 
the book have been determined by the availability of good 
general discussions of their subjects. Cell division (Chapter I) 
and the genetic basis of sex (Chapter III) have been treated 
at considerable length because of the general inadequacy of 
discussions of these subjects, while the treatment of the 
mechanism of heredity, available in many excellent accounts, 
is here greatly condensed. The present account starts with 
the single cell which each of us once was, and examines the 
conditions of its growth and reproduction. The next two 
chapters provide the historical setting for that cell, tracing its 
continuity with the earlier generation of cells and of beings 
that have provided its heritage. Next follows an analysis of 
the nature of development, a study of the complex interac- 
tions of gene with gene, of genes with cytoplasm, of organic 
part with part, of whole with part, and of all these with the 
various aspects of their environment. Finally comes a descrip- 
tive account of development, culminating in maturity and 
sinking at last into senility and death. With each man there 


perishes the unique assemblage of genes that along with the 
ever-varying environment made him what he was. But the 
genes themselves, cast into new arrays in the reproductive 
cells, are as immortal as life itself. 


The author desires to express his deep indebtedness to those 
who through counsel and assistance have aided in the prep- 
aration of this book: 

To the Administrative Officers of Stephens College for al- 
lowing the author a year's leave of absence, and thereby en- 
abling him to join the Bureau of Educational Research in 
Science at Teachers College, Columbia University, and com- 
mence planning and writing this volume. To Professor Sam- 
uel Ralph Powers, of Teachers College, Columbia University, 
Administrative Officer of the Bureau of Educational Re- 
search in Science, and to the author's colleagues in the Bu- 
reau, among them especially Dr. J. J. Schwab, of the Uni- 
versity of Chicago, and Professor Frederick L. Fitzpatrick, of 
Teachers College, Columbia University, for help in deter- 
mining the style, character, and scope of the book. To Pro- 
fessor E. W. Sinnott, of Yale University (formerly of Barnard 
College, Columbia University), for comments and sugges- 
tions of great value. For careful reading and criticism of 
certain chapters, to Dr. Kenneth Cooper, of Princeton Uni- 
versity (Chapter I), Dr. Tracy Sonneborn, of Johns Hopkins 
University and Indiana University (Chapter III), Dr. John 
Cameron, of the University of Missouri (Chapter V), Dr. 
Gairdner B. Moment, of Goucher College (Chapters IV-VI), 
and Dr. Herbert O. Elftman, of Columbia University. To 
Miss Charlotte V. Meeting, of the Bureau of Educational Re- 
search in Science, for editorial supervision and assistance in 
correspondence. To the many who have generously given per- 
mission to use the illustrations credited to them, and especially 
to Professor Otto Lous Mohr, of the University, Oslo, Nor- 


way, and to Professor Charles E. Metz, Dr. B. P. Kaufmarm, 
Dr. George L. Streeter, and Dr. C. H. Heuser, all of the Car- 
negie Institution of Washington, for supplying photographic 
prints. To Mr. Theodore Miller, who has drawn the original 
figures for this book, as well as the large number of borrowed 
illustrations that have been modified, and has thereby con- 
tributed no little to the style and appearance of the volume. 
Finally, to my wife, Suzanne Smith Glass, without whose un- 
failing encouragement, criticism, and assistance the work 
would never have reached its present form. 

In no case, of course, should any of these individuals be 
held responsible for the final expression of fact or opinion, 
which was determined by the author alone. 

Bentley Glass 
Baltimore, December 15, 1942 



Spontaneous generation may exist in the border- 
land between the living and the inanimate, but it 
occurs no higher in the scale of life, 2. Cells are 
formed by the division of pre-existing cells, a divi- 
sion essentially a transmission of the requisites for 
cell growth and development, 7. Cell division is 
actually a coordination of several semi-independent 
processes, 25. The cell in division should be con- 
sidered as a physical system, 31. Cell division is 
significantly affected by chemical substances, 38. Re- 
production at its simplest is cell division, 42. Illus- 
trations of the belief in spontaneous generation by 
two ancients and two men of the middle ages, 48. 
The relation of belief in spontaneous generation 
to the conflicting developmental theories of prefor- 
mation and epigenesis, 49. Pasteur on spontaneous 
generation, 50. Structure of glutathione, 52. 



Among the higher plants and animals, individuals 
usually arise by the fusion of two reproductive cells, 
53. In the maturation of the reproductive cells the 
chromosomes are shuffled and redealt in single sets, 
64. Hereditary variation arises primarily from per- 
manent changes in genes, 71. Potential variation in 
the individual hereditary pattern is a direct conse- 
quence of the nature of meiosis and syngamy, 80. 
Gene linkage and crossing over oppose each other in 
their effect upon variety among individuals, 103. 



The mechanism of sex produces variation among 
offspring, 121. Sexual reproduction results from the 
interlocking of sexual and reproductive cycles, 124. 
"In the beginning . . . male and female," 133. The 
sexes are next isolated, 138. In man and the higher 
animals, a complex balance of sex-determining genes 
is handled in a simple way by means of sex chromo- 
somes, 147. Genes carried in the sex chromosomes are 
inherited in an exceptional "sex-linked" fashion, 157. 



Genes interact to produce traits, 168. The products 
of genes interact in the cytoplasm, 180. The organ- 
ism during development reacts as an integrated 
whole, 190. Can we assess the relative importance of 
heredity and environment? 211. 



Cleavage— cell multiplication, 224. Growth begins— 
the hollow ball, 229. The hollow ball becomes a 
two-layer sack, 234. The middle layer— provision for 
specialized distribution, excretion, and movement, 
242. The membranes of the embryo— early provi- 
sion for our nourishment, respiration, excretion, 
and protection, 246. The development of form, 253. 
Adequate distribution— a circulatory system, 259. 
Adequate nutrition— a digestive system, 268. Ade- 
quate provision for breathing air— the respiratory 
system, 277. Adequate provision for eliminating 
wastes— the excretory system, 282. Adequate percep- 
tion of one's surroundings— the sense organs, 287. 
Adequate provision for adjustment, 301. Adequate 
provision for coordination— the nervous system, 316. 
Chemical correlation, 328. Provision for the future 
of the race— reproduction, 334. 


Until our prime, disease and accident are the main 
enemies of long life, 349. The complex mechanisms 
of our bodies eventually wear out, 357. 

INDEX 371 

Genes and the Man 


Life Begins — The Single Cell 

TO understand a man, we must know as much as possible 
of his past life. Today's actions and attitudes are rooted 
in early training; our childhood conceptions and beliefs, 
fashioned according to the pattern of our culture, persist in 
our adult behavior. This we all know. On the other hand, 
how few of us comprehend the nature of those fascinating 
processes of growth and development which lie back of our 
first conscious memories. Yet without this knowledge we can 
no more understand ourselves as we are today than we can 
comprehend the nature of our society and government with- 
out knowing something of the story of the settling of Amer- 
ica, the Revolution, the Civil War, and the expanding 

The mold of our social life is set ere we come on the 
scene; we may conform or rebel. However, it seems more 
intelligent to learn what this mold is in the light of how 
it came to be. For, though set, it is not unalterable; slowly 
in good times, often swiftly in evil, it can be changed by the 
pressure of circumstance; and understanding, we may play 
our part. So it is with our individual growth and develop- 
ment, too. From our parents we receive a hereditary pattern 
which largely determines our physical and mental nature, 
and which in the course of its realization is modified by 
whatever situations we meet. Every characteristic of an in- 
dividual can result only from the interaction of hereditary 


and environmental factors. The physical basis of our hered- 
ity is, indeed, determined from our life's beginning, but 
from that moment on our surroundings continuously exert 
their influence, sometimes strongly, sometimes with little ef- 
fect. The interplay of these contrasting factors is evident at 
every stage in the emergence of a man or a woman. 

As an individual develops, features appear which we can 
interpret only in the light of the past of our kind. Besides 
this, development commonly proceeds as though future 
needs were anticipated. As an embryo obviously can neither 
foresee its needs nor remember human history, such facts 
must mean that the racial pattern of heredity has itself been 
adapted to these needs, and very well adapted at that. 

Let us aim, therefore, to trace the interaction of the he- 
reditary pattern with the environment throughout the mount- 
ing complexities of growth and development, and, moreover, 
to interpret it in terms of our racial past and the goal of ma- 
ture fitness for the needs and activities of life. To unravel 
these myriad twisted and tangled threads, however, we must 
find their beginnings. What is the nature of an individual 
at the moment when his life begins? We can answer this only 
if we know in turn how an individual comes into existence. 
Our course must be first to treat the origin of the individual; 
next, his preformed nature, a matter of hereditary pattern. 
Only thereafter can we begin to describe and analyze the ac- 
tual processes of growth and development. 




Only in modern times has there come a realization that 
all individuals originate from previously existing individ- 
uals of the same general kind. The ancients, including even 
Aristotle, commonly believed that the lower forms of life, 
especially parasites and "vermin," sprang from slime or 


putrefying matter. (See Note A, p. 48.) The idea that such 
living forms might generate spontaneously was not even chal- 
lenged until the seventeenth century, and for two hundred 
years thereafter men's ideas on this matter seemed to depend 
chiefly upon whether they were religious or materialistic, or 
upon whether they leaned to one or another theory of re- 
production and development. (See Note B, p. 49.) 

It was not until our North and South were locked in 
civil war that Pasteur and Tyndall performed the experi- 
ments which showed that even the minutest living organ- 
isms, the bacteria which are associated with processes of 
putrefaction in nutrient fluids, are not formed spontane- 
ously from inanimate matter. Like dust, these organisms 
float in moving air, settling slowly whenever the air becomes 
still. If they chance to fall into a solution furnishing an 
abundant food supply, each germ can, in a few hours, pro- 
duce hundreds of millions of its kind. But if the air to which 
such solutions are exposed has been completely still so long 
that all dust and bacteria have settled, or if the air is filtered 
through cotton plugs, no bacteria can reach the fluids. By 
boiling the nutrient solutions after the containers have been 
plugged or by bending the open necks so that no germs can 
enter, putrefaction can be prevented indefinitely. (See Note 
C, p. 50.) 

Probably no experiment has had greater effect upon the 
welfare of mankind than this one! It has made possible the 
isolation and study of individual types of germs, and the 
elucidation of their relationship to disease; upon it modern 
bacteriology and medicine are founded. It has made possible 
the preservation of sterile conditions during operations, and 
thus surgery has been relieved of its once frightful aftermath 
of infection and death. Besides, when it was found that 
boiling the fluids was unnecessary and that heating to 6o°-65° 
C. for 20 to 30 minutes was sufficient to destroy nearly all the 
germs, particularly those causing disease, a method was avail- 
able for the treatment of milk which removes most of the 


bacteria without greatly altering its nutritive qualities. To this 
"pasteurization" method, now legally enforced in many cit- 
ies, we owe much of the great drop in infant mortality which 
has characterized the last five decades in Europe and the 
Americas. Countless thousands of babies once died of ty- 
phoid and other milk-borne diseases in their first year; now, 
fortunately, there is little danger from this source. 

Still, there were at first troublesome exceptions to the 
efficacy of these methods. Adherents of spontaneous genera- 
tion took new heart, for occasionally even the most carefully 
plugged and heated solutions putrefied. Alas for their views, 
further study soon led to the discovery that certain micro- 
organisms form very tough, resistant spores, able to with- 
stand great heat and afterward to germinate. To kill these 
and so to obtain perfectly sterile solutions, it is necessary only 
to reheat the solutions after the spores have had a chance to 
germinate. Accordingly, pasteurization was modified to in- 
clude two heat treatments separated by an interval of hours 
—a method now standard practice in canning foods. 

Pasteur 1 and others thus demonstrated to us that the liv- 
ing forms with which we are acquainted are not arising spon- 
taneously under conditions existing on the earth today. On 
the other hand, all indications point to the former presence 
upon the earth of conditions under which life as we know it 
simply could not have existed. At some time or other, then 
-perhaps more than once-life must have originated here. 2 

iThe efforts made by Pasteur to remove all possibility of belief in spon- 
taneous generation are recounted in the glowing tribute by his son-in-law, 
Rene Vallery-Radot. This life is one which should be read and reread by all 
even remotely interested in biology. (Vallery-Radot, R. The Life of Pasteur, 
Eng. trans. Doubleday, Page, New York, 1916.) 

2 We shall pass over those theories which hold that life has come to the 
earth in the form of spores floating through space, since they. merely remove 
our problem to another sphere. Life as we know it clearly depends for its 
existence upon such a concurrence of natural factors as is found on the earth 
today. (See P. B. Sears, Life and Environment. Bureau of Publications, 
Teachers College, Columbia University, New York, 1939.) Not only have we 
no indication of the existence of such a situation elsewhere, but even were 
there such a place, we should still have no notion of how life might have 
originated there any more readily than here. 


Is there any evidence as to how the chasm between the life- 
less and the living could have been bridged? 

The bacteriophages and filtrable viruses 3 seem indeed to 
stand in such a position. Until recently they have been re- 
garded by everyone as living. Like the parasitic bacteria, 
they multiply within the tissues of a particular plant or 
animal host, setting up specific disease conditions and stim- 
ulating extremely specific and lasting immunities. When 
they are exposed to x-rays, they are inactivated; the doses 
required to do this correspond closely to those which kill 
bacteria or spermatozoa. They are so small as to lie beyond 
the utmost power of our best microscopes, making it impos- 
sible for us to observe them individually, but their behavior 
is biologically just like that of the bacteria. 

On the other hand, there is mounting evidence to show 
that the bacteriophages and filtrable viruses are not alive. 
Instead of being a complex colloidal system, like protoplasm, 
at least some of them are single chemical molecules. This, 
of course, has long been indicated by their size, for while 
some almost reach the limit of microscopic visibility (200 m^), 
others, such as the virus of infantile paralysis, are no larger 
than some of the protein molecules (10 m/x). The evidence as 
to their molecular nature now seems conclusive. Dr. W. M. 
Stanley, of the Rockefeller Institute, and his collaborators 
have succeeded in isolating, by two quite different methods 
(chemical extraction and ultracentrifuging), 4 the virus that 
causes the tobacco mosaic disease. This virus proves to be a 

3 Bacteriophages prey upon specific bacteria, dissolving their colonies, 
while filtrable viruses produce such plant diseases as tobacco mosaic disease, 
tobacco ring spot, potato leaf roll, and peach yellows, and such animal and 
human diseases as measles, mumps, infantile paralysis, smallpox, rabies, 
yellow fever, typhus, fever blisters, and shingles. 

4 The ultracentrifuge is a high-speed centrifuge, capable of rotating mate- 
rials at upward of 60,000 revolutions per minute, and of developing a force 
well over 100,000 times that of gravity. Such forces will separate the compo- 
nent phases of a suspension or emulsion into layers (stratification), with the 
heaviest layer at the "bottom" and, in the order of their specific gravities 
(relative weights in comparison with that of an equal volume of water), the 
lighter layers above. 


protein crystal, of the greatest molecular size known (molecu- 
lar weight about 43,000,000). The crystals have lost none of 
the power of the original virus to produce the disease when 
inoculated into tobacco leaves; in fact, they are the virus. 5 
Other plant viruses and animal viruses have also been isolated 
by the ultracentrifuge, and they, too, turn out to be protein 
crystalline substances of huge molecular size. With the suc- 
cessful development of the electron microscope, the tobacco 
mosaic virus has been photographed. It appears to be a slen- 
der rodlike crystal, 280 rm* in length and 15 mju in each of its 
two other dimensions. Even the virus of influenza A, which 
is among the smallest of all known viruses, having a diameter 
of only 1 1 m^ and a nearly spherical shape, has had its pic- 
ture taken. 

Here are substances which, because they are monomolec- 
ular and crystalline, may well be classed as nonliving, but 
which behave like living organisms in a number of ways. It 
is not incredible that our knowledge of the chemical synthe- 
sis of organic compounds may continue to advance until 
viruses can be produced in the laboratory just as various vi- 
tamins and hormones are already being produced. Would 
this be the artificial production of life? And would our suc- 
cess make the occurrence of spontaneous generation seem 
any more probable? 

To understand what we are asking, we must raise once 
again the old question that has ever baffled man's persistent 
curiosity: What is "life"? What makes a thing "alive"? Can 
we at last begin to discern an answer? Life, perhaps, is not 
any one thing. It is a group of attributes, no doubt assem- 
bled one by one, which we constantly associate because we 
are most familiar with systems (plants and animals) iri which 
they occur together. Yet any one of these can be found by 
itself in some nonliving system. If, then, by the spontaneous 

5 For the proof of this point, Dr. Stanley received, in 1936, the prize of 
$1000 awarded annually by the American Association for the Advancement of 
Science for an especially outstanding paper among those presented at its 
Christmas session, 


generation of life we mean the simultaneous concurrence of 
all these attributes, the experiments of Pasteur answer us 
emphatically: No! But if we mean the emergence of any 
single characteristic, selected as of primary importance, may 
not the answer be different? 

Not least important among the attributes of life is the 
ability of a particular chemical molecule or group of mole- 
cules to duplicate itself repeatedly, a property which is 
known as autocatalysis. This multiplication can take place 
only under narrowly specific conditions. The raw materials 
needed for the synthesis must be present in the environment, 
and physical conditions must be appropriate. Certain en- 
zymes perhaps have this ability, and certainly the 'phages 
and viruses do; in other words, it is an ability that may be 
possessed by "nonliving" systems. Yet, as we shall see, this 
property of life is the very basis of reproduction. Remem- 
bering that individuals arise only through reproduction— 
that from generation to generation life is a continuum— one 
is tempted to say: Surely this is the basic attribute of life! 
Then, is not the chasm between living and nonliving 
bridged? Whatever our answer, at least our attention is di- 
rected forcefully to the nature of the reproductive processes. 




Although the theory that all plants and animals are com- 
posed of units called cells was proposed in 1838-1839, it was 
some time before there was any very good idea of how cells 
are formed. 6 By 1855, however, Virchow was able to sum up 

6 Actually, although Schleiden and Schwann have been almost universally 
credited as founders of the cell theory, others, notably Mirbel, Lamarck, 
Dutrochet, and Turpin, had expressed virtually the same ideas considerably 
earlier. It was merely the vigor with which Schleiden and Schwann advocated 
their views that marks the years 1838-1839 as the beginning of a new era in 
biological thought. As to their views on cell formation, they had most 
curious and erroneous ideas. Schwann, for example, believed that new cells 


many observations on the origin of cells by means of the di- 
vision of preexisting cells in the dictum: "Where a cell ex- 
ists there must have been a preexisting cell, just as the 
animal arises only from an animal and the plant only from 
a plant." 7 ''It is here that the full significance of the cell- 
theory for heredity and development first dawns upon us. 
If the cells of the body always arise by division of preexisting 
cells, all must be descended by division from the original 
germ-cell as their common ancestor; and such is the ob- 
served fact. . . . This critical point once made clear, the 
dominating significance of cell-division in the history of life 
began to stand forth in its true proportions." Cell division 
in an individual's development "is but an infinitesimal part 
of a greater series of cell-divisions that has no assignable 
limits in the past or future. The germ-cell arises by division 
of a cell preexisting in the body of the parent, and in its turn 
divides to form the body of the offspring [italics added by 
author] and also new germ-cells for coming generations; and 
so on without end. Embryologists thus arrived at the concep- 
tion ... of an unbroken series of cell-divisions that extends 
backwards from our own day throughout the entire past his- 
tory of life. So far as we know, life under existing conditions 
never arises de novo. It is a continuum, a never-ending 

usually arise by a sort of "crystallization" from a "formless moisture." For a 
recent consideration of the origins of the cell theory, see the paper "Cell and 
Protoplasm Concepts: Historical Account" by E. G. Conklin in The Cell and 
Protoplasm (American Association for the Advancement of Science, Science 
Press, Lancaster, Pa., 1940). 

7 The German pathologist, Rudolph von Virchow (1821-1902), was con- 
vinced that only through knowledge of the nature of the cell could light be 
thrown upon disease. This idea was lost sight of during the period when 
diseases were being traced to germs. Virchow himself bitterly opposed the 
advances made by the bacteriologists, and ended by dropping this work 
entirely and turning to archaeology and anthropology. Today medical men 
are beginning to realize that even where the specific external cause of a 
disease is known, they have grasped only one aspect of it. What the germ does 
to the cell, and what the cell does to defend itself, are just as vitally im- 
portant. Here we have a good example of the way in which many scientific 
ideas, born ahead of their time, eventually come into their own. The quoted 
sentence in the text is from Virchow's Cellularpathologie, p. 25 (1858). 


stream of protoplasm in the form of cells, maintained by 
assimilation, growth and division. The individual is but a 
passing eddy in the flow which vanishes and leaves no trace, 
while the general stream of life goes forwards." 8 

Since this unbroken series of cell divisions links genera- 
tion to generation, and a cell from the body of a parent di- 
vides to form the body of the offspring, all requisites for 
growth and development must be components of the cell. 
Reproduction is therefore essentially a contribution of these 
requisites by the parent cell to its cell offspring. What are 
the requisites? There must be, first, a complete set of those 
factors which control the specific composition and organiza- 
tion of living substance and the characteristic course of 
events in all the processes underlying growth and develop- 
ment; and second, a supply of the organized living substance 
capable of carrying on all essential activities, and often in- 
cluding certain specialized derivatives and a supply of food 
sufficient to maintain the organism until it is itself capable 
of securing more— that is, first, genes and second, protoplasm 9 

8 Wilson, E. B. The Cell in Development and Heredity, ed. 3, pp. 9-11 
(Macmillan, New York, 1925). The introduction to this great biological classic 
is superlative writing. Chapters IX, XI, and XII provide material on cell 
division, the individuality of the chromosomes, and their relation to heredity, 
which may well be consulted in connection with the present discussion. 

9 It is true that in general usage protoplasm, no doubt, includes also the 
genes, but in the absence of a word to designate extragenic protoplasm the 
present usage may be allowed. 

Living protoplasm is a complex system, perhaps best described as a 
colloidal sol, that is, a mixture of dispersed ultramicroscopic particles sus- 
pended in a fluid. In protoplasm the particles are chiefly protein and the 
fluid is a watery solution of various salts, sugars, and other soluble sub- 
stances. The colloidal sol is capable of a reversible change into a gel, in 
which the solid portion, or phase, of the system becomes a continuous 
meshwork, while the fluid phase may either be broken up into separate 
droplets or remain continuous. In protoplasm the solid phase itself has a 
strong affinity for the fluid phase, so that the gel can vary enormously in its 
fluid content and is highly elastic. The change from a sol to a gel is gradual, 
and is most apparent in the alteration of the viscosity (resistance to flow) of 
the mixture. Many important life activities appear to depend upon localized 
changes in viscosity within the cell, e. g., the locomotion of ameboid cells 
and the mechanics of mitosis (see pp. 35-37). Sol-gel reversibility is therefore 
of fundamental biological importance. External factors which affect it, such 


(plus foodstuffs, and so forth). Reproduction deals with the 
transfer of these essentials. 

What evidence have we that both of these classes of sub- 
stances are requisite? A very good indication that genes 
alone cannot survive and grow comes from the fate of the 
spermatozoon. Each sperm is made up of little more than 
a single tightly packed set of genes. Spermatozoa, however, 
are incapable of continued life, and die as soon as their 
stored supply of energy-yielding substances is exhausted. 
The spermatozoon that penetrates and fertilizes an egg, how- 
ever, as we shall see, absorbs substances and contributes its 
share to the control of growth and development. Like sperms, 
the tiny polar bodies thrown off by an egg (see p. 132) are in- 
capable of further development alone. Like the egg, they have 
a complete single set of genes, but they possess only a very 
small amount of active protoplasm and practically no stored 
food. Without protoplasm and foodstuffs genes must perish! 

But, an abundant supply of protoplasm and foodstuffs is 
apparently of no avail if the genes are absent. A geneless frag- 
ment of a cell usually succumbs quickly; in any event cells 
lacking genes, such as the red blood cells of mammals, can 
survive for a limited period only and cannot reproduce. As 
a rule, one set of genes seems sufficient to promote normal 
development, although with increasing sets there often goes 
an increase in size of both cell and organism. But in the 
higher organisms, the absence of any representative of even 
a single gene generally results in death or enfeeblement. It 
appears true that practically every gene native to an organism 
is essential to normal functioning for every one of its cells. 
Even an unbalance in the normal make-up of the gene com- 
plex is very injurious. Let but a few genes be present in more 
or less than their normal proportion and there may be a 
marked deleterious effect upon the individual. The battery 
of genes in an organism is a delicately adjusted system, the 

as temperature, hydrogen ion concentration (pH), and mechanical agitation 
(shaking and stirring), are consequently important too. 



parts of which are tuned to harmony with one another. One 
may double or triple the system without changing its balance, 
just as one may multiply both sides of an equation by the 
same factor without altering their equality; but one cannot 
add to or subtract from one side and not treat the other simi- 
larly without destroying the balance of the equation. 

Heredity results from the genetic continuity 
of dividing cells 

This idea August Weismann strenuously reiterated, until 
at last he ran the danger of carrying it too far. The funda- 
mental effects of the principle are, nevertheless, quite clear. 
No child inherits its characteristics from its parents' bodies 
(soma), but from their germ cells, and each of these in turn 
has descended in unbroken lineage from that one original 
cell, the fertilized egg or zygote, which by division gave 
rise to all the cells, somatic and germinal, of that parent. 
Therefore nothing that happens to the parent's body can be 
inherited, unless in some way the effect can be passed on to 
the germ cells, and these through their internal situation 
are usually well protected from external influences. To be 
sure, certain effects, such as those of alcohol or a change in 
climate, may reach them. However, in the course of time 
these effects wear off, although it may take a number of gen- 
erations. Only changes of the genes are known to be truly 
lasting, in a strict sense hereditary. So far as we know— and 
just about every imaginable way has been tried— genes can- 
not be affected indirectly. This fact shatters all theories of 
the inheritance of acquired characters. No parent should 
hope that his own education, or fear that his lack of it, can 
have the slightest effect upon the native intelligence of his 
offspring. No biologist can very consistently believe in the 
evolution of living organisms through any effort on their 
part to meet their needs or to satisfy their wants. 10 

10 This subject is discussed with unusual clarity in Chap. XV of H. S. 
Jennings' well-known book, The Biological Basis of Human Nature, pp. 329- 
358 (W. W. Norton, New York, 1930). 



Since there are many vitally necessary genes per cell, as we 
have indicated, the process of transmission must involve a 
duplication and a distribution of each one. The basic re- 
productive process is therefore that which brings about the 
qualitatively equal distribution of the genes. Now where 
are the genes? Clearly we must hunt for them in some quali- 
tative phase of cell division, that is, some phase which would 
distribute to each of the cell offspring identical sets of bodies. 
Knowledge of the actual mechanics of cell division fol- 
lowed a great development of the technical side of biology. 
Methods of killing, fixing, sectioning, and staining tissues 
made possible the accurate observation of cellular form and 
structure. A group of brilliant men in the thirty years from 
1870 to 1900 formulated our ideas of the physical basis of 
heredity and the mechanism of development. They observed 
carefully; they preferred sound reasoning to speculation; and 
important advances came thick and fast. Observing animal 
eggs, Fol was the first to see the rays that appear in the proto- 
plasm at opposite sides of the nuclear vesicle, making the 
star-shaped figures he called asters; and Butschli observed 
that, as the nuclear membrane disappeared, the rays stretched 
across it to form a spindle-shaped figure between the asters. 
In a plane through the middle of the spindle lay small grains 
or tiny rods, now known as chromosomes because they stain 
intensely. These were seen to split into two groups that 
moved toward opposite ends of the spindle, where, according 
to Oskar Hertwig, each is reconstructed into a typical nu- 
cleus. Strasburger extended the observation of these phe- 
nomena to plants, finding essentially the same behavior, ex- 
cept for the lack of asters. He made an additional discovery 
when he showed that before the spindle is formed the chro- 
mosomes are to be seen in the nucleus as long, twisted dou- 
ble threads, which later shorten and thicken. This was con- 
firmed for animal cells by Flemming, who also showed that 
the double strands come from a lengthwise splitting of each 
chromosome. The culmination of this series of researches 


was reached when van Beneden demonstrated that the chro- 
mosome halves, after being arranged upon the spindle, sep- 
arate, one strand of each chromosome passing to each pole. 

Division of the cells is completed by furrows which appear 
in the equatorial plane and deepen until the cells are com- 
pletely separated. In plants, however, a plate forms in this 
position, thickens, and becomes the dividing cell wall. Thus 
the cell substance surrounding the disintegrating spindle, 
with all the globules and grains of food suspended in it, is 
divided between the daughter cells. This division may be 
equal or very disproportionate, depending upon physical 
mechanisms which will be examined later. Evidently a gross 
quantitative division of the protoplasm is sufficient. 

To the group of men who worked out the nature of cell 
division— Fol, Butschli, Oskar Hertwig, Strasburger, Flem- 
ming, and van Beneden— and to others who, through technical 
advances, made their work possible, or who confirmed and 
extended their observations to hundreds of plants and ani- 
mals, we owe a discovery which deserves to rank in impor- 
tance with those other great biological discoveries of their 
day: Pasteur's discovery of the causation of disease by bac- 
teria, Mendel's discovery of the basic laws of heredity, and 
Darwin's epochal enunciation of natural selection as a basis 
of evolution. How often while honoring such a lone genius 
as Mendel we forget others whose cooperative and cumula- 
tive labors have proved no less outstanding, men like these 
whose discovery of the mode of cell division is fundamental 
to our understanding of reproduction, heredity, growth, and 
development. 11 

As this process of chromosome division and distribution, 
which was named mitosis, proved to be of nearly universal 
occurrence, the significance of a division that is qualitatively, 
rather than quantitatively, equal was perceived. What sub- 

11 See E. Nordenskiold, The History of Biology, Eng. trans., Knopf, New 
York, 1928, Tudor, New York, 1935; and W. A. Locy, Biology and Its Makers, 
ed. 3, Holt, New York, 1915. Nordenskiold is more scholarly, but Locy's book 
is better illustrated. 


stance, except that carrying the hereditary properties, asked 
Roux, the father of experimental embryology, and Hertwig 
and Strasburger, could be of such importance as to require so 
meticulously equal a distribution? 

The chromosomes have persistent individuality 

There remained one great objection to assigning to the 
chromosomes leading roles in the drama of heredity. They 
vanish! At the close of each mitotic division, they disappear 
from view, and during the relatively long "interphase," last- 
ing until the beginning of the next division, only isolated 
granules of their component chromatin are visible in the 
stained nucleus. The demonstration that chromosomes per- 
sist from one cell generation to the next, whether lost to 
view or not, is primarily due to the long continued research 
of Boveri. He succeeded in showing that the number of 
chromosomes reappearing after the interphase is regularly 
the same as the number of chromosomes disappearing at its 
beginning. In Ascaris, for instance, if the two chromosomes 
of the egg become separated, they will form two small nuclei 
instead of a single larger one, and after the interphase one 
chromosome will reappear in each. In other forms, both 
plant and animal, it has been shown repeatedly that when- 
ever the chromosome number becomes accidentally altered 
the new number persists indefinitely. 

A broader aspect of this same principle is the constant 
number of the chromosomes in the cells of a particular race. 
Each form of life investigated, whether plant or animal, has 
been found to have a characteristic number of chromosomes 
in each cell nucleus, a number ranging from two (in Ascaris 
megalocephala, the horse roundworm) to 200-208 (in various 
species of the crayfish, Cambarus). In man the number is 
forty-eight. In two animals, a bug and a mite, the character- 
istic number has been traced through every stage of develop- 
ment and into every tissue. 12 

12 Too much importance, however, should not be attached to these numbers. 
Closely related forms often have very different numbers, while the same nam- 


Another type of evidence is also very significant. -In As- 
caris the chromosomes are very long and their tips project in 
lobes from the surface of the nucleus. These lobes persist 
during the interphase, and when the chromosomes reappear 
their ends project into them just as before. In a certain 
grasshopper the chromosomes also form separate lobes, while 
one of them retains its identity even further, forming a sep- 
arate nucleus pressed against the larger one. In certain cells 
of a minnow (Fundulus) and a snail (Crepidula) the chro- 
mosomes never fuse completely, but each forms essentially a 
separate nucleus during interphase. 13 

Most striking of all is the case of a protozoan described by 
Belaf. Here cell divisions succeed one another so rapidly 
that before the enormously long chromosomes have been 
fully separated to their "tails," their "heads" begin to take 

ber occurs in widely different species. Thus a snail, an ant, various rodents, 
and several plants as diverse as a brown alga and members of the banana, 
lily, crowfoot, violet, and composite families share the chromosome number 
of man, while among the rats and mice we find such a variety as 40, 42, 48, 
50, 52, and 54. The honeybee is another sort of exception, as males have 
16 chromosomes and females 32. (See Chap. Ill, p. 129.) 

The basic chromosome number may also be multiplied in single cells or in 
tissues within one individual. This multiplication may take place through frag- 
mentation of large chromosomes into tiny ones, a condition which occurs in As- 
caris, where the two chromosomes found in the germ cells separate into about 
sixty in somatic tissues. (Conversely, two or more chromosomes may combine 
and act, either for a time or permanently, as a unit.) Still more common is 
doubling due to the division of the chromosomes without an accompanying 
division of either nucleus or cytoplasm, so that all the daughter chromosomes 
remain in one nucleus within one cell. This is especially frequent in cells 
that are old and highly specialized. In a number of species of fruit fly (Dro- 
sophila), for example, the number of chromosomes in the tracheal cells is 
regularly double the usual somatic number, and in the rectal glands the 
number is redoubled. Doubling may be brought about by exposure to cold 
or chemical agents during mitosis, and it is notably abundant in degenerat- 
ing cells. In mosquito pupae, intestinal cells degenerating during metamor- 
phosis have been seen with 6, 9, 12, 18, 24, 36, and 72 chromosomes, where 
the characteristic number is 12. Cells of cancerous tissue often have giant 
nuclei, or several nuclei in each cell, due to a similar duplication of the 
chromosomes without cell division. 

is This condition also occurs in a strain of maize. Here it is known to be 
due to the action of a single gene, a first instance of the control of the genes 
themselves over the character and behavior of the chromosomes. 



part in a subsequent division. The chromosomes being sep- 
arated on the spindles of the secondary divisions are still as- 
sociated for most of their length, and at their farther ends 
are still entwined with their duplicates in the sister cell (see 
Fig. i). As there is an interphase between these divisions, 
the very association compels us to see a morphological con- 
tinuity of the chromosomes through the interphase. 

*^5^~^*& r ' su^l^a 



Fig i Two pairs of enormously long chromosomes in the protozoan Aggre- 
gaia eberthi involved in two cell divisions at once. Their "heads" are passing 
fhrough a second cell division before their "tails" are completely separated 
after the first division. (Redrawn after Belaf) 

The persistent individuality of the chromosomes is also 
shown in the way in which differences in their size and form 
are passed on from cell generation to cell generation, being 
transmitted regularly and characteristically to each of the 
cells of the organism, and on to successive generations of 
individuals. Chromosomes vary principally in length. They 
are as a rule, globules or rods or shaped like V's or J's. 
Constancy in their size and form has now been observed in 
a very great number of plants and animals. 

Unusual types, such as the bent-tipped chromosome found 
in a certain locust, have also persisted in cell generation after 
cell generation. In 1922 some female fruit flies were discov- 
ered in which two rod-shaped chromosomes had become at- 
tached to each other at one end, forming a V. This stock 
(called attached-X) has been widely used by geneticists all 


over the world, and the new chromosome has now persisted 
for more than 500 generations. 

When chromosomes are exposed to x-rays, they may be 
broken and reconstructed in various ways. If a piece is bro- 
ken out of the middle of a chromosome, or off its end, 
it may be visibly shortened, depending upon the size of the 
lost piece. When two chromosomes break simultaneously, 
pieces are frequently interchanged; and if these are not of 
the same size, the chromosomes are altered in size and shape 
(Fig. 2). These chromosomal abnormalities are all per ma- 



Fig. 2. A, the normal chromosomes of the female fruit fly (Drosophila melano- 
gaster). (From Mohr) B, chromosomes of the female Drosophila following 
breakage and reconstruction. One of the longer Y-shaped chromosomes (5) 
has lost a piece that has become attached to one of the small globular 
chromosomes. The chromosomes marked X are those that determine the sex 
of the individual. (From Dobzhansky) 

jwrii^jmd are transmitted from parent to offspring, from cell 

In the salivary gland cells of flies the individuality of the 
chromosomes is demonstrated to the highest degree. Here 
are giant chromosomes, thousands of times greater in volume 
than those in ordinary somatic or germinal cells, which can 
yet be identified with the tiny ones present in other cells of 
the fly. They are banded with hundreds of rings, some 
dense, some light, some solid, some mere rows of faint dots. 
Each chromosome has its characteristic pattern of bands, and 
each minute section is identifiable (Fig. 3). These patterns 
persist through generation after generation, so that even each 
small segment of every chromosome has its own persistent 




Fig 3. The giant salivary gland chromosomes of the fruit fly (Drosophila 
melanogaster), magnification about 600 diameters. Inset, the same chromo- 
somes as they appear at the same magnification in most body and germ cells. 
(Courtesy of B. P. Kaufmann, Carnegie Institution of Washington) 

What do all these things show? Even if they fail to dem- 
onstrate indubitably that the genes are in the chromosomes, 
they make it an extremely plausible assumption. The per- 
sistent individuality of the chromosomes, even to their mi- 
nutest segments; the longitudinal cleavage of each chromo- 
some in mitosis, which results in the duplication of each one 
of these segments; and the accurate distribution to each of 
the cell offspring of an identical set-these characteristics cer- 
tainly appear to provide the qualitatively equal division of the 
genes for which we were looking. The final demonstration of 
this point rests upon the fact that the behavior of the chromo- 
somes in every case exactly parallels that of the hereditary traits. 
This can be made clear only when we understand more fully 
the role of sex in reproduction, which will be treated in 
Chapter II. However, we may now plausibly assume that the 


genes are located in the chromosomes. As we keep this fact 
in mind, we shall find that the fundamental importance of 
the nature of cell division becomes increasingly clear. 

All mitotic cell divisions are essentially alike 

In another book of this series, The Development of Our 
Ideas Concerning the Physical World, 14 Duane Roller says: 
"Both the permanent aspects and the changes occurring in 
phenomena must eventually be studied if our picture of na- 
ture is to be of most value, but the permanent aspects are 
usually much the easier to observe and treat. ... It is a very 
essential part of the method of these sciences to search for 
quantities that remain constant amid the variations of na- 
ture, for laws that prevail, for concepts that can be retained 
as permanent. In a less conscious and less systematic way, 
even our ordinary thinking is permeated with this quest for 
factors in our environment which we can regard as remain- 
ing the same from day to day; for things we can 'count on'; 
for values we can accept as permanent. Without such self- 
created reference points for thought and action, existence in 
this world of incessant and complex change is unthinkable." 
Here, in the processes of cell division, we may find such a con- 
stant biological factor, for the permanency and the stability of 
life-forms rest squarely upon the duplication and equal distri- 
bution of the genes at cell division. The resemblance of off- 
spring to their parents, which we no doubt take as much for 
granted as we do the assumption that an unsupported object 
will fall, depends upon the nature of mitosis. Heredity very 
likely means to us mainly a transmission of variable traits, 
such as eye color, skin color, resistance to disease, intelli- 
gence, and so on. These are of no little immediate im- 
portance to us. They may determine our social group, our 
occupation, our health, our mate; they may even be a matter 
of life or death to us. But before variation, there must be 
something to vary from! The essence of heredity lies rather 

1 4 Unpublished, 1943. 



in the statement that all creatures bring forth "after their 
kind" (Gen. 1:21). This is due to the mechanism of mitosis, 
which is essentially alike in all living forms. Only from an 
understanding of this mechanism for maintaining the sta- 
bility, the status quo, of life-forms can we start to investigate 
hereditary variation. 

The process of cell division varies in cells and organisms 
in an extraordinary number of minor ways, both in the form 
of the components of the mitotic figures and in their be- 
havior. Nevertheless, this manifold variety can be classified 
and reduced to a number of types, all linked by transitions. 
"This circumstance stands as one of the strongest supports of 
the theory that all mitotic cell divisions are processes essen- 
tially like." 15 And the essential likeness of all forms of mi- 
totic cell division is a most striking witness to the funda- 
mental unity of all living forms. To understand the 
situation, therefore, it is necessary only to take one example, 
and compare it with the other main types. 

In white blood cells of the salamander, the nucleus during 
interphase contains only a few lumps and nodes of dark- 
staining chromatin and is otherwise clear and homogeneous. 
In the cytoplasm lies the centrosome, a clear gelled area with 
two minute granules in it (Fig. 4). 

The first signs of approaching cell division are seen in the 
nucleus. In the homogeneous plasm there form long threads, 
twisted and coiled, and staining deeply with nuclear stains. 
These are the chromosomes. The nucleus swells somewhat. 
(At this point the nucleus has entered the prophase stage.) 
As mitosis progresses, the chromosomes become shorter, 
thicker, and less coiled, and it is then noticeable that each is 
really composed of two threads, very closely applied to each 

is This remark by K. Belaf is translated from Die cytologischen Grundlagen 
der Vererbung, p. 32. (Gebriider Borntraeger, Berlin, 1928.) For those who 
read German, this is the most complete and best survey yet made of the 
cytological bases of heredity. The description here given of mitosis in the 
salamander is paraphrased from it (pp. 28-32). Belaf's death in his early 
prime, as a result of an automobile accident near Los Angeles, was a severe 
loss to science. 


other. Each chromosome is bent, rather like a hairpin, and 
the flexures lie close to, or even against, the nuclear mem- 
brane. Meanwhile the centrosome has moved to the middle 
of the cell, and the two granules (known as centrioles) have 
separated a bit as the gel surrounding them liquefies. As 
they move apart, rays appear radiating from them into the 
cytoplasm, rays which mingle among themselves to produce 
a clear area, spindle-shaped. These are the asters and the 
spindle; and both together are called the amphiaster. The 
spindle area grows larger in every dimension as the centro- 
somes move farther apart, and is traversed by a myriad of 
very delicate fibers running from one pole to the other, those 
on the periphery curved, the central ones straight. The chro- 
mosomes are already lying against the face of the nucleus 
touching the growing spindle. As the nuclear membrane 
breaks down, they are drawn into an irregular ring, the flex- 
ure of each chromosome imbedded in the surface of the 
spindle. (At this point prophase merges into metaphase.) 

The ring of chromosomes is next flattened, until the im- 
bedded parts lie approximately in a plane (the equatorial 
plane) perpendicular to the axis of the spindle. In clear 
cases, it is possible to see that a mantle of fine fibers (mantle 
fibers) surrounds the central spindle, and connects the flex- 
ures of the chromosomes with the centrosomes (see also Fig. 
5A). The rays of the asters have now reached their maximum 
size, extending to the periphery of the cell. 

For a brief time the chromosomes remain fixed in the 
ring. Then the halves of each separate and move toward the 
poles of the spindle, flexures preceding, ends trailing. It is 
as though they were being pulled apart and toward the poles 
by the mantle fibers, "inserted" at the flexures. The central 
spindle lengthens as the chromosomes separate. (This stage 
is the anaphase.) 

Short of reaching the centrosomes, the two groups of chro- 
mosomes halt. (The mitosis now enters the telophase stage.) 
Within each group the chromosomes press together, until 



their limits are made out only with difficulty. The spindle 
fibers then disappear; the centrioles divide, each aster dim- 
ming and then reappearing as they do so. Next a membrane 
surrounds each group of chromosomes, forming daughter 
nuclei. These swell in size, and as the chromosomes alter 
chemically so that they stain less and less, vacuoles appear 


Fig. 4. Cell division in the white blood cells of a salamander (Salamandra 
maculosa), a-c, e, i, I, and p are polar views; the remainder are views from 
the side, a, interphase; a convoluted nucleus surrounding a central mass of 
cytoplasm in which is the centrosome. b-c, early prophase, d, beginnings of 
the formation of the central spindle, e-g, transition to metaphase. h-i, meta- 
phase. j-l, anaphase, m-p, telophase. (In the polar views of the equatorial 
and daughter rings not all of the twenty-four chromosomes are visible.) 
Magnification about 825 diameters. (From Belaf's Die cytologischen Grund- 
lagen der Vererbung). 

between them. Their outlines grow vague. Projections ex- 
tend out and form bridges uniting them, until finally, in the 
typical interphase nuclei, only knots of chromatin betray the 
former arrangement of the chromosomes (Fig. 4). 

In general, the time consumed by mitosis varies consider- 
ably with external factors, but thirty minutes to an hour is 
perhaps average. It is more important to have some idea of 


the relative lengths of the stages. These are approximately 









However, the stages have different temperature characteris- 
tics; that is, they vary in relative length at different tempera- 
tures. They also appear to vary in relative length in different 

More frequently studied is the rate at which mitoses suc- 
ceed one another, a rate which determines the duration of 
each cell generation. This is what is generally meant by the 
terms mitotic rate and rate of cell division, and they are so 
used in this chapter (see pp. 3 8 "42)- 

The two principal variations from the preceding type 

In the first of these variants no central (cytoplasmic) spin- 
dle is formed by the centrosomes. The true spindle, made of 

A B 

Fig. 5. A, chromosomes arranged in a ring around the central spindle. A 
salamander cell. (Fankhouser. Courtesy o£ the Journal of Heredity) B, 
chromosomes arranged in a plate across the true spindle. A human cell. The 
smallest chromosome, the one called the Y, is found only in males. (Evans 
and Swezy. Courtesy of the Journal of Heredity) 



nuclear material, instead of surrounding the central spindle 
like a mantle, completely takes its place. The chromosomes, 
instead of forming a ring, then form a "plate" extending all 
the way across the equatorial plane of the spindle (Fig. 5.6). 
In the second variant, there is again only a true spindle of 
nuclear material, but in addition there are no visible centro- 
somes or asters. This latter form of mitosis occurs almost 


Fig. 6. Cell division in the onion (Allium cepa). Observe the characteristic 
barrel-shaped spindle and the absence of centrosomes and asters, a, inter- 
phase, b-c, prophase, d-e, transition to metaphase. f, metaphase. g-i, 
anaphase, j-l, telophase. Magnification about 825 diameters. (From Belaf's 
Die cytologischen Grundlagen der Vererbung) 

universally in the higher plants; it is common in unicellular 
organisms, and it is characteristic of the two divisions by 
which the eggs of higher animals become mature (Fig. 6). 

In the completion of cell division through division of the 
cytoplasm there are two principal types. In most animal cells 
a furrow appears on the cell surface in the equatorial plane 
of the spindle, during telophase. As the spindle dissolves, the 
furrow deepens and the cell is pinched in two. In most 
plant cells, however, granules form an equatorial plate upon 


the spindle. They increase in size and coalesce, and the plate 
grows to the margins of the cell. The deposition of salts, pec- 
tin, cellulose, and lignin then commences, until finally the 
typical double cell wall, each half including two or three dis- 
tinct layers, is completed. The two major types of cytoplas- 
mic division are linked by a transitional form found in the 
algae, so that their difference is not radical but merely an 
accompaniment of the rigid cell wall of cellulose produced 
by most plants. The essential result is ever the same: the cy- 
toplasm is divided between the daughter cells, and whatever 
specialized cell structures lie in it, such as plastids in plants, 
and various sorts of rodlike or minute globular bodies found 
in animal cells, are separated into two more or less equal 

groups. 16 


Thus far we have described cell division as a series of 
events. Actually, however, it consists of three closely coordi- 
nated processes. The changes in the chromosomes are largely 
independent of spindle formation; and both, in turn, are in- 
dependent of the division of the cytoplasm. A critical analy- 
sis of these will enable us to distinguish the elements that are 
of fundamental significance. Incidentally, it will furnish a 
fine example of the complexity of biologic processes, of the 
numerous interrelations which must be synchronized and co- 
ordinated for what might seem at first the attainment of a 
simple end. Mitosis, as described in textbooks, is frequently 
oversimplified. We should be on our guard lest we take a 
very superficial knowledge for real understanding. 

In the first place, chromosomes may, on occasion, divide 
without any division of the other elements of the cell. Now 
the formation of these daughter chromosomes is merely the 

16 An exception is found in the centrosomes, which, since they lie at the 
poles of the spindles, are always distributed equally. 


visible aspect of this first phase of all division; the reduplica- 
tion of the genes themselves is the initial step. At some time 
between one anaphase and the succeeding prophase— some 
observers claim even in the preceding prophase— the chromo- 
some becomes visibly double. Has the single string of genes 
absorbed at each locus 17 the appropriate chemical substances 
from the nuclear substrate, synthesizing them into the form 
and pattern of each gene, until the amount of each is suffi- 
cient to form two? Or does each gene by a sort of selective 
crystallization form a twin beside itself? These questions de- 
pend largely on the very nature of the gene itself; for if it is 
composed of a number of molecules, the first method of re- 
duplication will be more probable, while if it is a single 
molecule, the second is to be preferred. The latter view fits 
the present scanty experimental data somewhat better. 

Without entering the realm of speculation, however, we 
can draw two important conclusions about gene reproduc- 
tion. In the first place, the duplication of all the genes takes 
place simultaneously; the processes are in some way synchro- 
nized. This is a significant addition to the original property 
of autocatalysis we observed in the viruses. Second, the di- 
vision of the genes, and consequently of the chromosomes, 
takes place long before any other phase of cell division be- 
gins. The chromosomes always seem to be split at least one 
division ahead of their partition and occasionally, perhaps, 
even earlier. In anaphase and in the following prophase, 
when the chromosomes are not too condensed, they are often 
spirally coiled, and sometimes this coil, called the chromo- 
nema, can be distinguished from a surrounding matrix. It is 
this chromonema which is split in preparation for the suc- 
ceeding mitosis and, no doubt, contains the genes. 

Since chromosome duplication so far precedes the other 
phases of cell division, it is probably valid to regard it as the 
usual initiator of the next phase. However, synchronization 

17 The term locus is used to indicate the position of a gene in the chromo- 


may break down at this point, so that, on the one hand, genes 
may divide repeatedly without disjoining, and, on the other, 
spindles may form over and over in the absence of any chro- 
mosomes whatsoever. The division of the chromosomes 
without their distribution may be an abnormal feature of 
development, as when the spindle mechanism is paralyzed by 
colchicine, 18 or it may be a perfectly normal one, such as oc- 
curs in certain tissues of fruit flies or mosquito larvae. In 
either case the divided chromosomes remain in a cluster, and 
the number of chromosomes within the cell is doubled. 

The changes in form of the chromosomes during mitosis 
may be included in this first phase, although seemingly their 
sole function is to reduce the diffuse chromosomes of the in- 
terphase to a compact form capable of disjunction upon a 
spindle. During prophase the changes consist of (1) an altera- 
tion of chemical state, and (2) condensation and contraction. 
At this stage the one or more nucleoli, each associated with 
special formative regions of particular chromosomes, com- 
mence to shrink. As probably their material is distributed to 
the associated chromosomes, contributing to the matrix which 
grows up around the invisible gene string, the nucleoli thus 
disappear while the chromosomes grow thicker and stain pro- 
gressively darker. 19 

is The action of colchicine is especially potent and is already of great 
practical value in plant breeding. Because it stops the course of mitosis in 
metaphase, the split chromosomes, failing to disjoin, are frequently all re- 
incorporated in a single nucleus. Thus tetraploid cells arise, which may give 
rise vegetatively to more vigorous plants with larger or more numerous fruits 
or doubled flowers. Especially interesting is the possibility of obtaining fertile 
hybrids. Most hybrids, as is well known, are sterile, but by inducing a dou- 
bling of the chromosome number a fertile hybrid carrying two sets of chromo- 
somes from each of the parent species may be procured. One can hardly over- 
estimate the enticing possibilities in the field of hybridization this method 
holds out. Already new types of cotton and tobacco, as well as a number of 
fruits, have been produced by its means. 

19 Change in staining capacity indicates a change in chemical nature, since 
it takes an acid substance to react with the basic (alkaline) dyes which stain 
chromatin so densely. The acids of the nucleus (nucleic acids) are found 
nowhere else in nature, except in elementary organisms such as bacteria, 
where nucleus and cytoplasm are not differentiated. 


The chemical alterations and the condensation of the chro- 
mosomes are, then, mainly changes of the matrix in which 
the strings of genes are imbedded. The double coil of the 
chromonema is simply compressed until its strands are no 
longer visibly separate. At the end of prophase each chromo- 
some is really double, although its strands are so closely com- 
pressed and intertwined as to appear single. In metaphase 
the splits reappear and the chromosomes then disjoin. 

In some cases either whole chromosomes or large portions 
may remain darkly staining during interphase, or may make 
their appearance ahead of the other chromosomes as pro- 
phase sets in. In Drosophila those portions of the set of chro- 
mosomes which vanish in the customary way carry practically 
all the genes, and the visibly persistent regions are genetically 
barren like the nucleolus. We should therefore distinguish 
carefully between the chromosomes and the actual strings of 
genes. The chromosomes contain much nongenic material, 
which coalesces about the genes during mitosis. Since the 
nongenic regions carry the points of spindle attachment, we 
may assume that the dark-staining chromatin is the portion 
of the chromosome coordinating it with the second phase of 
mitosis— spindle formation and chromosome disjunction. 

The second semi-independent phase of cell division is con- 
cerned with the disjunction of the chromosomes and involves 
the formation of a spindle. That it can be relatively inde- 
pendent of the chromosomal changes is clear from the follow- 
ing facts: (1) When, by chemical or mechanical treatment, all 
the chromosomes are induced to go to one pole, spindles 
continue to form in the daughter cell that lacks chromo- 
somes. Their formation keeps step with the mitoses in the 
adjacent nucleated cells. (2) With needles, a skillful man can 
extract the entire nucleus from a cell. Spindle formation 
goes steadily on. (3) A number of chemical compounds 
(carbon dioxide, quinine, ethyl ether, hydrogen sulfide, po- 
tassium cyanide, colchicine) inhibit this phase without seem- 
ing to affect gene and chromosome division. 


In thinking of spindle formation we should carefully dis- 
tinguish between the true and the accessory spindles. The 
true spindle, which brings about the disjunction of the chro- 
mosomes, is mainly or wholly nuclear in origin. It is often the 
sole spindle, but whenever an accessory spindle is present, the 
true spindle surrounds it, as we have noticed, like a mantle. 
The fibers of the accessory spindle, which connect the two 
centrosomes, have been observed indenting the nuclear mem- 
brane and leading to its dissolution. Otherwise the accessory 
spindle seems of little importance. It may even be present or 
absent in cells of the same organism (axolotl). The evidence 
cited above concerning the independence of spindle forma- 
tion from gene and chromosome division applies both to the 
accessory spindle (1 and 2) and to the true spindle (3). 

Why do the chromosomes move toward the poles of the 
spindle? Genetic evidence is convincing that each chromo- 
some is attached to the spindle by a single structure (its so- 
called spindle attachment point, or centromere). Whenever a 
chromosome suffers breakage, the resulting fragment that lacks 
such a structure becomes lost unless reattached; otherwise it 
will not be drawn onto the spindle nor is it likely to be in- 
cluded in either one of the two daughter nuclei. 20 Some force, 
evident from the relation between the position of the spindle 
attachment and the shape of the chromosomes, must act upon 
these points. This does not necessarily imply that the chromo- 
somes are drawn to the poles by the contraction of spindle 
fibers. Spindle fibers are not typical elastic fibers, for they do 
not appear to thicken as they become shorter. In the living 
cell, in fact, no actual spindle fibers can be seen. They are 
perhaps no more than lines of stress indicating a linear orien- 
tation of molecules from pole to pole, such an orientation as is 
known to occur in fibrous proteins like keratin, the ma- 
terial of our nails and hair. Or perhaps the apparent fibers 

20 The chromosomes of bugs (Hemiptera) seem to form an exception to this 
general rule. In some, perhaps in all, species of this order the chromosomes 
have no single spindle attachment point, and fragments behave like inde- 
pendent chromosomes. 


merely indicate that the water in the spindle is unevenly 
distributed and lies in axial channels between the more rigid 
portions of the spindle. In at least one organism, a locust 
(Stenobothrus), the movement o£ the chromosomes is evi- 
dently due to a rapid growth of the spindle between the 
planes where the two sets of chromosomes are imbedded. 
This growth pushes the chromosomes and the poles farther 
apart. It is likely that this may be a rather general mecha- 
nism, for the distance chromosomes move is frequently pro- 
portional to the size of the spindle, which lengthens as the 
chromosomes disjoin. In Sciara, the fungus gnat, a very un- 
usual occurrence takes place. At one division in the forma- 
tion of male reproductive cells, a half-spindle is formed, with 
the attachments of all the chromosomes directed toward it. 
Nevertheless, certain chromosomes move away from the sin- 
gle pole of the spindle along the diverging rays of the half- 
spindle. Evidences of tension in the chromosomes seem to 
imply that their spindle attachments are still attracted to the 
single pole, but that some superior force carries them in the 
opposite direction. This superior force may reside either in 
the chromosome itself or in the surrounding island of spin- 
dle material which accompanies each chromosome through 
the cytoplasm. 

All in all, the evidence does not lead to any clear or simple 
interpretation. The most satisfactory explanation is perhaps 
that, to start with, there is an autonomous repulsion of the 
chromosomes. This is followed by an expansion of the cen- 
tral spindle material, pushing the two groups of chromosomes 
farther apart, and a contraction of the two distal portions of 
the spindle, drawing the chromosomes closer to the poles. 
Other factors still to be revealed may also play an important 
part in the disjunction of the chromosomes, that crux of 
the second phase of cell division. 

The third and final phase of cell division is concerned with 
the distribution of the remainder of the essentials for cell 
growth and development to the daughter cells. This phase 


is also semi-independent. Both chromosomes and nucleus di- 
vide commonly enough without any division of the cyto- 
plasm, whenever the activity of the latter is much lowered, as 
by the inclusion of large amounts of inert food material, or 
by lack of oxygen, low temperature, a change in the concen- 
tration of the surrounding medium, shock, or treatment with 
such chemicals as lactic and pyruvic acids. On the other 
hand, cytoplasmic divisions may follow one another in regu- 
lar succession through the stages of early development in cells 
entirely lacking nuclei and forming asters but not spindles. 
The partition of the cytoplasm, in contrast to that of the 
genes, is gross and only approximately instead of exactly equal. 
The more important cell structures clump around the spindle, 
structures such as the plastids in plant cells, and the rodlike 
or globular bodies (chondriosomes, mitochondria) found in 
animal cells and believed to be associated with oxidations. 
Then, as previously described, in plants a cell plate forms 
across the spindle and continues to extend until it separates 
the two daughter cells. These, however, remain attached by 
their walls of secreted cellulose. In animals and in the ma- 
turing reproductive cells in plants, the separation is per- 
formed by a constriction of the cell in the equatorial plane 
of the spindle. The cells, under the control of genetic fac- 
tors, then either adhere or separate. In the latter event, we 
observe the characteristic type of cytoplasmic cleavage by 
which the fission of one-celled animals is accomplished. 


Having now described how the essential structures are ap- 
portioned in cell division, we should not forget that, like all 
life-processes, cell division is dynamic. The cell is the sphere 
of action of complex interacting forces. Still ignorant as to 
what these are, we can, nevertheless, learn something of their 
distribution and nature from the very configuration of the 


cell, both external and internal, and from the changes we 
have described as taking place. 

To begin with, the typical isolated cell is spherical; "that 
is to say, the uniform surface tension at its boundary is bal- 
anced by the outward resistance of uniform forces within." 
The uniformity of the forces within the cell depends upon 
the degree of fluidity of the protoplasm. When protoplasmic 
colloids gel, their fluidity is greatly diminished, and forces at 
work reach equilibrium more slowly. The spherical shape 
may thus be distorted. Accordingly, whenever the surface 
tension fluctuates or varies locally, the cell may pulsate, as a 
trout's egg does, or protrude in finger-like projections, as do 

ameboid cells. 

For the same reason the nucleus is also spherical, and be- 
cause its fluid cytoplasmic surroundings are more constant 
than the external environment of the cell, it preserves its 
shape more constantly. Whenever, in the course of differ- 
entiation, the consistency of the cytoplasm alters and becomes 
more solid, the shape of the nucleus becomes correspond- 
ingly elongated. There must be, however, some difference m 
surface tension between the nuclear content and the sur- 
rounding cytoplasm. If this "phase difference" were too 
slight, the nucleus could not cohere on account of the low 
surface tension, 21 and would break up into smaller units. 
Just such scattered nuclear material is found in many rhizo- 
pods, and a similar situation leads to the bursting of the con- 
tractile vacuoles of fresh-water protozoans. Conversely, nu- 
clear material tends to aggregate within the limit of surface 
tension, and separate nuclei in a cell may thus often draw 
together and fuse. 

Any interchange of materials between the cell and its en- 

20a Thompson, D'Arcy. On Growth and Form, p. 164. Ca ™ brid ^™ f 
versity Press, 1917. This book is the great well-spring of the modern study of 
ornwrh as related to form. (New edition, 1942.) . 

8 Tf he su ace tension between two phase, is the difference between .hen 
average cohesion, or tendency of like particles to together, and the 
adhesion, or attraction, of the unlike particles of the two phases. 


vironment must take place through the surface membrane of 
the cell, while the living substance to be maintained is sub- 
stantially its volume. Consequently the relations between 
the surface area and the volume of a cell are of great impor- 
tance. Now as a cell grows, its volume (4/3 Jtr 3 ) increases far 
more rapidly than its surface area (4m 2 ). This automatically 
puts an upper limit to cell size, at a point where the transfer 
of materials through the membrane is barely adequate to 
satisfy the needs of the protoplasm. (Of course, cells may ap- 
parently transgress such limits through the inclusion of large 
amounts of inert material, such as stored food.) Long ago it 
was suggested that, since the cell, upon reaching this size, 
must either quit growing or divide, the primary impetus to 
cell division lay here. There is some support for this view. 
Studies of the ameba have shown that the attainment of a 
particular cell volume— more specifically of a definite nuclear 
volume— is, in this animal, a prime factor in initiating mi- 
tosis. However, many a cell divides before attaining its maxi- 
mum size, and in rapidly growing tissues the multiplying 
cells are nearly always relatively tiny. We may therefore ac- 
cept the idea that a maximal cell size is imposed by the 
surface area/volume ratio, without regarding it as more than 
an accessory factor in initiating cell division. 

Of other factors that may be involved in initiating mitosis, 
we have almost no idea. What underlies autocatalysis, and 
especially what synchronizes the genes in this activity— these 
remain major mysteries. Nor do we know how the duplica- 
tion -of the gene strings normally sets going the formation of 
a spindle. 

The centrosomes have often been regarded as autonomous 
dynamic centers of spindle formation. In animal cells we 
can see them dividing at anaphase in preparation for the 
succeeding mitosis, almost as early as the genes themselves. 
We can also see the asters and the accessory spindle, when it 
is present, forming around and between the centrosomes as 
they move apart, while in cells where the centrosomes lie far 


from the nucleus to begin with, either they or the nucleus 
migrate until they reach their usual position. Unquestion- 
ably the true spindle is oriented by the centrosomes, and 
when they are absent it is not pointed but barrel-shaped. 
Plurality of the centrosomes also throws light on their role. 
When several sperms manage to penetrate an egg, each of 
them bringing in a centrosome, multipolar spindles form and 
the chromosomes are distributed irregularly. 

Yet there seems to be no necessity for regarding the centro- 
somes as possessing genetic continuity like that of the chro- 
mosomes. They may arise in nonnucleated fragments of eggs 
treated with hypertonic solutions, 22 or centrifuged, where 
the original centrosomes have remained in the nucleated 
portion. It has recently been found that the chromosomes of 
certain snails can lose their centromeres (spindle attachments), 
and that these structures then turn into extra centrosomes (or 
centrioles) that go on dividing in rhythm with the centro- 
meres of the other chromosomes. This discovery makes it 
apparent that the centrosomes of the spindle and the centro- 
meres of all the chromosomes are similar structures, prob- 
ably related in origin. It may be that the relationship be- 
tween them is expressed in the orientation by the centrosomes 
of the movements of the chromosomes toward the poles. 

Whether centrosomes are present or not, the completed 
true spindle is itself bipolar. The centrosomes, then, must at 
least represent visibly the dynamic centers at the poles of the 
spindle. This they orient and give a more pointed shape. 
The most striking evidence that the centrosome may actually 
be the dynamic center is that, when it fails to divide, 
monotfers-half-spindles-are formed, and the chromosomes, 
though duplicating normally, fail to separate far (except in 
Sciara, as previously discussed), and consequently become in- 
cluded in a single nucleus. Since divisions with or without 

22 In comparing the concentrations of a solution inside and outside a cell, 
hypertonic indicates that the dissolved substance is more concentrated out- 
side than inside. 


centrosomes can occur even in the same organism, it seems 
probable that the difference is mainly between a defined and 
visible dynamic center of spindle formation in one instance, 
and a diffuse and indistinguishable one in the other. 

We speak of a dynamic center, and certainly the mitotic 
figure must be a field of some definite sort of force. Few 
have failed to be struck by its similarity to a bipolar mag- 
netic or electrostatic field. Yet the polarization is really not 
of this type, as the consistency with which asters repel one 
another shows; when separated they always move farther 
apart than when they are connected by a spindle. 23 Other 
types of forces, electrokinetic or osmotic, have been sug- 
gested as the mitotic force; but while each theory can be sup- 
ported by certain facts, there is at present little ground for 
choosing between them. 24 

Instead of theorizing on the basis of what may be only 
superficial resemblances, it might well be more fruitful to 
see what definite physical changes occur in the cell as it 
undergoes division. There is, for example, a great increase 
in the viscosity of the protoplasm. This is clear in comparing 
the unfertilized eggs of the sea urchin, or similar forms, with 
just-fertilized eggs in mitosis. The former have little resist- 
ance to being stratified by the centrifuge and, when pieces of 
glass are dropped on them, burst readily. But the eggs in 
mitosis strongly resist stratification, and if they burst at all 
under pressure, the viscous contents ooze out slowly. Arti- 
ficial agents which can stimulate mitosis in unfertilized eggs 
also cause the cytoplasm to gel. Concentrations of salt either 
lower or higher than those in the cell can do this and fur- 
nish us with a clue. For it is proteins of the globulin type 

23 Opposite magnetic or electrostatic poles form a field like an amphiaster, 
but attract one another. 

24 Full treatment of the various theories of mitotic force and the facts bear- 
ing on them is to be found in E. B. Wilson, The Cell in Development and 
Heredity, ed. 3, Chap. II, pp. 174-199 (Macmillan, New York, 1925); and in 
James Gray, Textbook of Experimental Cytology, Chap. 8, pp. 155-173 (Mac- 
millan, New York, 1931). A more recent review is that of F. Schrader, "The 
Present Status of Mitosis," American Naturalist, Vol. 74, pp. 25-33, 1 94°- 


which coagulate in this characteristic way; and globulins 
coagulated by heat or chemicals make realistic amphiasters. 

The coagulation of the protoplasm during mitosis is not, 
however, uniform throughout the cell. The periphery is 
more solidly gelled, forming a tough ectoplasm; the whole 
amphiaster is also a gel. Within the more fluid cytoplasm, 
spindle and asters, carrying the imbedded chromosomes, can 
be pushed about as a whole by a microdissection needle. 
The gel is so stable and so elastic that the amphiaster may be 
greatly distorted, pulled and even twisted into a spiral, with- 
out destruction; but too extensive tearing brings about its 
reversion to the sol state. Ordinarily the mitotic figure tends 
to orient itself in the greatest dimension of the cell, which is 
the most stable position for a semisolid suspended in a more 
fluid medium. 

Cleavage by deepening furrows and constriction is almost 
always associated with the type of mitosis in which there are 
definite centrosomes and asters at the poles of the spindles. 
Changes in viscosity play a part here as in spindle formation, 
so it is not surprising to find that carbon dioxide, which al- 
ters the hydrogen ion concentration, and so affects sol-gel 
reversibility, has a profound effect on both spindle formation 
and cleavage; or that high osmotic concentrations dissolve 
both spindle and asters irreversibly, thus checking both chro- 
mosome disjunction and cytoplasmic division; or that other 
chemicals have an effect upon both, which is reversible when 
not too severe. 

While the major part of each aster is firmly gelled, the cen- 
trosomes are clear and fluid. The thin tapering rays of the 
asters are also fluid, and along them the plasma flows in to- 
ward the centrosomes, where it accumulates. This can be 
readily detected, for the centrosome steadily increases in size, 
and solid particles or oil droplets introduced into the rays 
migrate toward it. The bulk of each aster consists of the 
cytoplasm between the rays. This is most strongly coagulated 
next to the centrosome, and peripherally grows progressively 


more fluid. The growth of the asters depends upon the area 
over which they can extend— this can be shown by cutting an 
egg into fragments when the asters are still small— and the 
position and depth of the cleavage-furrow in turn vary with 
the size of the asters. 

Yet after all, asters are not absolutely necessary to constric- 
tion. This is especially clear in isolated cells, such as white 
blood cells or certain kinds of cells growing in tissue-culture, 
which have no asters but which, nevertheless, divide by con- 
striction. First, they become ellipsoidal. Then, as the equato- 
rial constriction appears, blisters are extruded and resorbed 
at the poles, and currents flow superficially from the poles to 
the equator, where they turn inward and flow back to the 
poles. These blisters and currents are just what would be set 
up by a lowering of surface tension at the point closest to each 
pole, or by an increase of surface tension along the equator. 
The change in surface tension may be due to the approach 
of the reconstructed nuclei to the surface of the cell. The 
completion of fission appears, from studies of amebas and 
tissue-culture cells, to be essentially locomotory. The two 
halves simply crawl in opposite directions until they part 
company! In the absence of asters, constriction is therefore 
probably due to a change in the surface tension of the cell, 
followed by locomotion. 

In cells with asters the outer layer is clear and tough, and 
much less fluid than the underlying cytoplasm. It collects at 
the equator, and, according to at least one series of observa- 
tions, actually grows in toward the center of the spindle. 
Hence it serves much as do the cell plate and cell wall of 
plant cells, holding the two daughter cells together, although 
without their rigidity. Without doubt, therefore, the asters 
are connected with the mechanics of cytoplasmic division in 
cells which remain associated. 25 

25 The chapter by Robert Chambers in the General Cytology edited by 
E. V. Cowdry (University of Chicago Press, 1924) deals with the microdissec- 
tion analysis of the physical structure of the cell, during mitosis as well as in 
the interphase. It is somewhat out of date and needs to be supplemented. 



The role of chemical substances in stimulating cell divi- 
sion has been indicated in a number of observations. Mitosis 
in tissue cells is speeded up by foreign blood serum; in white 
blood cells by bacilli. Malignant tumor cells produce a sub- 
stance stimulating the mitotic activity of tumor tissues, and 
substances found in the vascular bundles of plants promote 
cell division in the healing of plant wounds. A cluster of 
cells of common origin has a marked tendency to divide syn- 
chronously. The general tendency of undifferentiated cells 
to divide rapidly, but to slow down and acquire different 
rates of division as they age and specialize, also indicates the 
presence of chemical factors which control the occurrence of 

Certain substances have been found which markedly affect 
growth in plants, either by stimulation or by inhibition. 
Three of these growth hormones, or auxins, as they are 
called, are known at. present, namely, auxin a, auxin b, and 
heteroauxin. They are complex organic acids. Though they 
affect growth chiefly by cell enlargement (see Chapter IV, p. 
197), auxin a and heteroauxin also stimulate cell division, 
both in primary and in secondary growth. 26 However, to do 
this requires concentrations some ten thousand times greater 
than those to stimulate cell enlargement, and such concen- 
trations almost certainly do not occur normally in cells. We 
may therefore well regard the effects of auxin and hetero- 

Gray (op. cit.) is excellent, though biased slightly by his own views of the 
mechanism of cytoplasmic cleavage. Chapter IX and the first part of Chap. 
X (to p. 150) of T. H. Morgan, Experimental Embryology (Columbia Univer- 
sity Press, 1927) are also good. More recent are L. V. Heilbrunn, An Outline 
of General Physiology, Chaps. VIII and XLII (W. B. Saunders, Philadelphia, 
1937), and W. Seifriz, Protoplasm (McGraw-Hill, New York, 1936). 

26 Primary growth in a plant is that which takes place at growing tips 
(meristem) in young tissues, such as embryonic root and plumule, root tips, 
and buds of all kinds. Secondary growth is that which increases the diameter 
of roots and stems through the activity of the cambium layer. 


auxin on cell division as a sort of indirect chemical stimula- 
tion. Since the processes comprising cell division and those 
prerequisite to it are extremely complex, and the substances 
involved are legion, it is not surprising that many substances 
can be found, especially those affecting general metabolism 
and oxidative rates, which also influence mitosis. Among 
these, besides the auxins, are other hormones such as adren- 
alin and insulin, organic acids such as acetic and citric acids, 
salts such as sodium chloride, and sugars such as levulose. 

Among the elements known to be essential to life is sulfur. 
In the cell this element is combined chiefly with hydrogen, 
forming what is called the sulfhydryl group (-SH) attached to 
some organic combination. Chief sulfur-supplying constitu- 
ent of an adequate diet is the amino acid, cystine. In cystine 
two sulfur atoms are linked to each other and to organic 
groupings, so that, if we symbolize the latter in general by R, 
cystine can be represented as R— S— S— R. Cystine is easily re- 
duced to two molecules of cysteine, which is accordingly 
R-SH. Either cysteine or cystine combines with two other 
amino acids to form glutathione, which therefore exists in two 
states R-SH and R-S-S-R (see Note D, p. 52). Now gluta- 
thione (R-SH) is present in most, if not all, living cells. 
It is one of the basic chemical substances upon which life de- 
pends; and the characteristics of life must to some degree 
depend upon its chemical properties. Its distribution in rap- 
idly growing tissues, such as the root tip of an onion or a 
regenerating segment of the hydroid animal Obelia, cor- 
responds to the intensity of metabolic activities (oxygen 
consumption, carbon dioxide production, reducing power of 
tissues, cellular electric potentials). 27 It is therefore highly 

27 Metabolism is customarily denned as the sum of all chemical and physical 
changes taking place in an organism, yet it is generally used in a much more 
restricted sense, for the definition just given is virtually synonymous with 
life and is so inclusive as to be well-nigh meaningless. However, all of these 
activities either release energy or require it; and since nearly all synthetic 
activities, with the exception of the photosynthesis carried on by green 
plants, get their energy from the oxidations which are the energy-releasing 
processes in nearly all organisms, the intracellular oxidations may be taken 


significant that glutathione, in either form, and perhaps 
other organic compounds of the R-SH type, too, stimulate 
mitosis in plant and animal cells. 

The importance of sulfhydryl in controlling mitosis is 
shown by the following instances: (1) In the absence of sulfur 
in the environment, the rate of fission of a protozoan (Chi- 
lomonas) diminishes rapidly until death occurs. This slow- 
ing up of the rate of division seems due to the rapid decrease 
in internal sulfur per cell, as fission proceeds and the existing 
store is thereby steadily halved. The stimulating effect of the 
sulfhydryl upon mitosis is greatest at a certain optimum con- 
centration, both above and below which it lessens. (2) In 
the ameba, cell volume (and especially nuclear volume) is, 
as we have noticed, a prime factor in controlling the rate of 
mitosis. Glutathione causes the nucleus to attain the opti- 
mum size for mitosis more rapidly. Thus nuclear division is 
stimulated, although cytoplasmic division does not always 
follow. (3) Copper and lead inhibit nuclear growth and di- 
vision, presumably by reacting with sulfur and breaking up 
the -SH group. (4) The rate of cell division is positively 
correlated with potential size in rabbits, and potential racial 

as a measure of the entire metabolism. This has naturally led to a narrower 
usage of metabolism, in the sense of the oxidations going on in an organism 
and their more immediate consequences. 

The total rate of oxidation in an organism or tissue can be measured by 
the amount of oxygen it consumes. Measurement by the amount of carbon 
dioxide produced involves an assumption that all oxidations are carried to 
completion, but as a rule the method may not be seriously in error. Meas- 
urement of the amount of water produced is inaccurate because of the small 
likelihood that all of it will be eliminated, at any rate promptly. (The same 
objection would naturally apply to the measurement of carbon-dioxide produc- 
tion in a green plant, in the presence of light.) For every oxidation there must 
be a complementary reduction, so that measurement of the reducing power of 
a tissue is equivalent to measuring its oxidative capacity. Finally, the rate 
of oxidation may be estimated from the amount of some form of energy 
produced. Heat is always released, and a considerable proportion of the total 
energy is thus lost, but comparative heat production is very likely a better 
measure of the efficiency of different tissues or organisms than of their rela- 
tive total oxidations. Electric energy also appears to be universally produced 
in cells, but opinion today is still sharply divided as to whether it is directly 
related to cellular oxidation or not. 


size is similarly correlated with the glutathione content of 
the newborn rabbit. (5) The hairlessness of hairless rats is 
due to a gene that also renders its carriers unable to produce 
cysteine (R-SH) from cystine (R-S-S-R). The hairlessness 
is very likely a secondary result of the chemical defect, being 
produced by way of the influence of the latter over cell 
division. Thus the last two instances indicate that certain 
genes control cell division through this chemical mechanism. 

Although we can detect no change in heat production 
either as interphase gives way to mitosis or during the prog- 
ress of mitosis, there is a clear-cut fluctuation in oxygen con- 
sumption, which has been correlated with changes in the 
concentration of the R-SH glutathione. This must mean 
that the interphase and the several phases of mitosis really 
differ in metabolic state. A further sign is that mitosis, like 
all metabolic processes, is retarded by cold, and the tempera- 
ture coefficients, 28 which are of the order of those of chemical 
processes, vary from stage to stage (highest in prophase; low- 
est in anaphase). 

But although the oxygen consumption changes during mi- 
tosis, this does not prove that cell oxidations control mitosis. 
As a matter of fact, many substances which affect respiration 
—carbon monoxide, for example— do not affect cell division 
at all. On the other hand, the events of cell division seem to 
influence the rate of oxidations rather than the reverse. 
Whether, then, the effect of glutathione upon cell division is 
independent of its role as an oxidative enzyme, or whether, 
as is more likely, the two roles are in some manner inter- 
related, and, if so, how— the answer will certainly be of major 
importance to our understanding of life. 29 

28 The temperature coefficient of any process is the number of times the 
rate of the process increases for each rise of io° C. 

29 On the sulfhydryl problem, only original papers are available. The 
rather contrary views of Hammett and of Mast and Pace should be com- 
pared critically. The former has written a great deal, but the essence of his 
ideas can be obtained in the one paper listed here. His views have been 
severely criticized by a number of workers. 

See Hammett, F. S. "The Natural Chemical Equilibrium Regulative of 


After careful observation, the similarities and dissimilari- 
ties of the mitotic cycle in hundreds of forms have today 
been summed up, and any possibility that purely descriptive 
morphology can throw further light on its nature is largely 
exhausted. For a deeper understanding of the intricate na- 
ture of cell division, we must turn to biophysics and bio- 
chemistry. Already a beginning-very tentative and uncer- 
tain, to be sure, but still a beginning— has been made. 


For the thousands of varieties of plants and animals which 
live as single cells, the process of mitosis and cytoplasmic di- 
vision, followed by separation of the two newly formed cells, 
is reproduction. The Paramecium and the ameba, the dia- 
tom and the desmid through this fission multiply at as- 
tounding rates. This throws a great deal of light on such 
basic life phenomena as sex, variation, and natural death! 
Sex, which we have perhaps considered almost a synonym 
for reproduction, is here divorced from it entirely. Even in 
protozoa, where a sexual process (conjugation) does occur, it 
seems to be quite unnecessary, for in one laboratory some 
20,000 generations of Paramecia have been raised without it, 
by fission alone. In the evolution of life, sex must be a rel- 
ative newcomer in comparison with reproduction. While it 
is true that we can see no mitosis in the smallest of all living 
forms, the bacteria, we do see fission there; and the elaborate 
mechanisms of mitosis for the distribution of genes, proto- 
plasm, and foodstuffs may well be unnecessary in so simple 
a form. Even here, however, we must suppose that the abil- 
ity of certain protein molecules to duplicate themselves is 
present. Given a suitable substrate, such as protoplasm, 
each such molecule can become two where it was but one! 

Growth by Increase in Cell Number," Protoplasma, Vol. 11, pp. 382-411. 1930. 
Mast S O and Pace, D. M. "Relation between Sulfur in Various Chemi- 
cal Forms and the Rate of Growth in the Colorless Flagellate, Chilomonas 
Paramecium," Protoplasma, Vol. 23, pp. 297-325. 1935. 


This is like the protein molecule of the virus, which can 
also duplicate itself under appropriate conditions, although 
otherwise it cannot. This duplication is, then, the very es- 
sence of reproduction, coeval with, perhaps even preceding, 
the origin of life itself. 

What is the extent of individual variation under these cir- 
cumstances? Clearly enough, since each chromosome is split 
and each gene duplicated, and since each cell receives a com- 
plete set, the sets of genes carried by offspring produced by fis- 
sion must be identical. If we begin by isolating a single organ- 
ism, the continuation of this process of cell division will soon 
result in a whole race of individuals carrying identical genes. 
Such a race is called a clone. Whatever variation occurs in a 
clone, provided the genes remain stable, must result solely 
from differences in the environment to which the indi- 
viduals are exposed; and, were they to live together within 
a completely uniform environment, both they and their de- 
scendants would manifest no variety whatever. They would 
form a race of individuals much more alike than two 
identical twins among mankind. Attempts have been made 
to split up such clones into races which would perpetuate 
through heredity the variations resulting from the environ- 
ment, but they have all been unsuccessful. For example, 
H. S. Jennings, of Johns Hopkins University, by selecting 
large and small Paramecia in a pure race, tried to estab- 
lish different stocks which would maintain these differ- 
ences, but to no avail. Large and small alike had progeny of 
the same average size. The same was true for reproductive 
rate and for resistance to heat or chemicals. Other men have 
had no better fortune in trying selection within pure lines of 
bacteria or yeasts. 

In plants which will grow from cuttings of stems, roots, or 
other vegetative parts, and in such animals as reproduce by 
budding or fission, or in which females produce daughters 
from unfertilized eggs, descendants carry sets of genes iden- 
tical with those present in their ancestors, and pure lines may 



be propagated. Here again, selection within the pure line fails 
to establish races hereditarily different. This has been tried 
in Hydra, plant lice, the lower Crustacea, and in many other 
forms. So well recognized is the principle in plant breeding 
that florists and horticulturists have long made a general 
practice of propagating their valued strains vegetatively. 

In the higher animals, pure lines cannot exist, but fission 
may occur during the development of a fertilized egg. Either at 
the two-celled stage or later, an embryo may divide into two 
or more separate parts, each of which becomes an individual. 
This phenomenon will be considered in other aspects later, 
but here we may note the practical identity of such individ- 
uals—not with either of their parents, to be sure, but with 
one another— whether armadillo quadruplets or Dionne quin- 

And what of death? Is there among the one-celled or- 
ganisms no ageing, no wearing out of the protoplasm or of the 
genes? The answer seems to be that cells removed from an 
organism can grow, divide, and grow again in a ceaseless 
cycle as long as external conditions are suitable. The cells 
may even attain a certain degree of differentiation, and cling 
together in a loosely organized, simple tissue. The famous 
cells from a chicken's heart have been living and growing in 
this way for thirty years since the culture was originally 
started by Alexis Carrel. Their protoplasm does not die; 
it is simply divided among the daughter cells. 

Protoplasm does not die because as it wears out it is renewed. 
There is a constant exchange of materials between environ- 
ment and cytoplasm. Foods, including oxygen, enter the cell; 
wastes, including carbon dioxide, leave it. Yet this metabolic 
activity of itself seems no more to produce ageing and death 
than the vortical whirling of water, in a basin into which it 
is running steadily from a tap and from which it is carried 
off equally steadily by the drain, results in exhaustion and 
end. Senescence and mortality in the cell appear rather to 
depend on three things. The primary cause appears to be 


specialization. In the higher organisms this takes the form of 
an aggregation of "specialist" cells. The aggregation is nat- 
urally attended by an increasing difficulty in maintaining for 
all cells a regular supply of foodstuffs and a regular removal 
of wastes. Thus the cell is gradually choked by its own prod- 
ucts and is slowly starved. We pay the price of death for the 
division of labor in our bodies. Our complexity is our 
doom. 30 

As the division of labor among a group of cells increases, 
the reproductive function itself is restricted to fewer and 
fewer of their total number. This is well illustrated in the 
members of the Volvox order, simple types at the bottom of 
the plant kingdom. Chlorogonium (Fig. 7 A) is at first a sin- 
gle cell, bearing at one end two whiplike lashes (flagella) 
with which it swims, and containing a number of chloro- 
plasts enabling it to carry on photosynthesis. By cell divi- 
sion, this individual becomes two cells; then the two, four. 
However, as a capsule is secreted around the first individual, 
the four are not entirely independent, but are confined for a 
time (Fig. 7U). Eventually the capsule bursts, and each of the 
four is set free to repeat the cycle. Here, evidently, the ca- 
pacity to reproduce is not limited. Each of the four is re- 
productive, and, if we think of the group as the individual, 
each cell is a spore, or reproductive cell. Pleodorina is like 
Chlorogonium, except that the process of cell division within 
the secreted capsule continues until there are 32-128 cells in 
all (Fig. 7C, D). These are all much alike, resembling the 
Chlorogonium individual, except that those at one end of 
the colony are smaller than the others. When the capsule 
ruptures, all but these small cells can form new colonies by 
cell division; but the small cells, solely vegetative, perish! 
Volvox is much larger yet, with more than a thousand cells ar- 
ranged over the surface of a great spherical capsule (Fig. >]E). 

30 The first two chapters in H. S. Jennings' book Life and Death, Heredity 
and Evolution in Unicellular Organisms (Richard G. Badger, Boston, 1920) 
deal with these questions, and are extremely thought-provoking. 

4 6 


'"'": '-'-,' ; -v 

G ' ■' , . 

B , *' 

0" -"-- 



Fig. 7. The simplest division of labor among cells, that of the vegetative and 
reproductive functions, as seen among green flagellates of the Volvox order, 
not drawn to scale. A, Chlorogonium, a solitary individual. B, Chlorogonium, 
a group of four, undifferentiated. C, the colonial form Pleodorina illinoisen- 
sis, with four small solely vegetative anterior cells and twenty-eight large 
reproductive posterior cells. D, Pleodorina californica, with relatively more 
vegetative cells and fewer reproductive cells. E, Volvox. Each cell is located 
in a hexagonal zone of the gelatinous sphere, and communicates with its 
neighbors by fine strands of protoplasm. There are relatively few of the 
larger reproductive cells and very numerous tiny vegetative ones. Daughter 
colonies are developing within the mother sphere. (A and B redrawn from 
Hartmann; C, D, and E, redrawn from Plunkett's Elements of Biology. 
Courtesy of Henry Holt and Company) 


The reproductive function is here limited to about a third 
of the cells in one half of the colony. These can drop down 
into the center of the hollow ball, and form daughter colo- 
nies, small spheres within the larger one. 31 Eventually they 
are set free when the parent colony, grown old, ruptures and 

The power to form reproductive cells (whether spores or 
sexual gametes) is still further limited in the higher plants 
and animals, where it is confined to definite reproductive 
organs. With the advent of cell aggregation and differenti- 
ation there is a progressive decrease in the proportion of 
cells that retain the capacity to produce a new individual 
when isolated from the organism. Cells which specialize upon 
other functions lose this power. 

The isolated cell or one-celled plant or animal possesses all 
the general capacities of the specialized cells of an organism 
such as man, who is billions of times greater and indescrib- 
ably more complex; but its capacities are not developed to 
the fullest. The protoplasm flows around food material, di- 
gestive enzymes are secreted, the liquefied food matter is 
absorbed and transported to all parts of the cell by diffu- 
sion and by currents. Oxygen enters the cell, the foods 
are oxidized to yield up their energy, or are synthesized to 
become constituents of the protoplasm; wastes are formed 
and excreted through the cell membrane. The released en- 
ergy appears in various forms— heat, light, electricity, chem- 
ical energy, mechanical work. These are controlled and 
coordinated, so that behavior is related to environmental 
stimuli. The course of differentiation consists of progressive 
specialization by certain cells upon some one of these ac- 
tivities. The processes of differentiation are controlled by 
the genes; and the nature of the genie pattern responsible for 
the multifarious variety of life will be considered more fully 
in Chapter II. 

si Sexual reproductive cells (gametes) are also produced. 

4 8 





Lucretius: "Even now there come out of the ground animals 

(99-55 b.c.) which are brought forth by the rain or the warm 
exhalations of the sun." {Be Rerum Natura) 

Vergil: "Kill an ox two years of age, whose young horns 

are just beginning to curl upon his brow, place 
him in a narrow enclosure strewed with leaves 
of thyme and rosemary freshly gathered, and 
soon from this fermenting humor there rises a 
swarm, which fills the air like rain from summer 

Paracelsus: "Let the sperm of a man by itself be putrefied 

(1490-1541) in a gourd glass, sealed up, with the highest de- 
gree of putrefaction in horse-dung, for the space 
of forty days, or so long until it begins to be 
alive, move, and stir, which may easily be seen. 
After this time it will be something like a man, 
yet transparent, and without a body. Now after 
this, if it be every day warily, and prudently 
nourished and fed with the arcanum of man's 
blood, and be for the space of forty weeks kept 
in a constant, equal heat of horse-dung, it will 
become a true, and living infant, having all the 
members of an infant, which is born of a woman, 
but it will be far less. This we call Homunculus 
or artificial man. . . . Now this is one of the 
greatest secrets, that God ever made known to 
mortal, sinful man." Comments Cole: "Paracel- 
sus disliked woman, which may explain his at- 
tempt to produce a foetus without the coopera- 
tion of a mother." 

Van Helmont: A recipe for procuring rats. . . . "All that is re- 
(1577-1644) quired is to cork up a pot containing corn with 
a dirty shirt; after about twenty-one days a fer- 
ment coming from the dirty shirt combines with 
the effluvium from the wheat, the grains of which 



are turned into rats, not minute or puny, but 
vigorous and full of activity." 32 


Swammerdam, in the seventeenth century, seems to have been 
the first to deny the spontaneous generation of life. Redi, a Flor- 
entine physician of the same period, had demonstrated conclu- 
sively that maggots appear in decaying meat only when flies have 
access to it. Harvey, his British contemporary, who discovered 
the circulation of the blood, was able through keen observation 
of the developing embryos of mammals, birds, and lower types, 
to conclude rather sententiously: "All animals, even those that 
produce their young alive, including man himself, are evolved 
out of the egg." Yet neither Redi nor Harvey could quite free 
himself of the belief that such tiny creatures as internal parasites 
and various sorts of insects arise de novo. Harvey, studying the 
development of the chick within the egg, concluded, like Aristotle, 
that organs arise successively by differentiation from the unspe- 
cialized substances of the egg. 

Swammerdam, on the contrary, greatly influenced against this 
epigenetic view by his investigations of the development of in- 
sects, saw in them a gradual unfolding of pre-existing parts. Sper- 
matozoa had only recently been discovered, and the famed Dutch 
microscopist, Leeuwenhoek, believed that life itself came from 
the male through the spermatozoon, while the egg furnished only 
nourishment and capacity to develop. Swammerdam's preforma- 
tion theory, in spite of subsequent distortion by factions con- 
tending for supremacy of egg or sperm, was the first attempt to 
subject ontogeny to natural law, to explain development in me- 
chanical terms. 

For the next two hundred years, however, the question of the 
existence of a spontaneous generation of organisms was closely 
tied to the controversy between the preformationists and the epi- 
genesists. The latter began to prevail following the insistence by 
Wolff (1759) that the earliest phases of development can actually 
be seen microscopically and are totally inconsistent with any 

32 Cole, F. J. Early Theories of Sexual Generation. Oxford University Press, 
1930. Here is a book full of interest to those who take zest in tracing the 
growth of our modern conceptions. The preformationist-epigenesist con- 
troversy is well covered. 


theory of preformation. With the discovery of the mammalian 
egg and the mode of its growth within the ovary by von Baer in 
1828, epigenesis was generally accepted. The discredit of the pre- 
formationist ideas was accompanied by a resurgence in the belief 
in abiogenesis (spontaneous generation). As microscopes im- 
proved, the myriads of bacteria, microscopic plants and animals 
present in the waters became evident in almost innumerable va- 
riety. Their life cycles were too difficult to trace with the meth- 
ods and equipment of the time, and they had a way of inevitably 
turning up in any situation where there was a food supply. 
Many, indeed, believed that the origin of these in vessels which 
had been free of them was actually proved. These things explain 
the scorn and vehemence met by Pasteur when, in i860, he put 
forward the claim that he had demonstrated that even these mi 
nute forms arise from organisms already present. 


In his lecture before the Sorbonne, on April 7, 1864, Pasteur 
summed up his crucial experiment in these words: "Here, gentle- 
men, is an infusion of organic matter of perfect limpidity, limpid 
as distilled water, and extremely alterable. It has been prepared 
today. Even tomorrow it will contain animalculae, little infu- 
sorians or flocculi of molds. 

"I place a portion of this infusion of organic matter in a flask 
with a long neck, like this one. Suppose I boil the liquid and 
then let it cool. At the end of some days, molds or infusorian 
animalculae will have developed in the liquid. By boiling, I 
have destroyed any germs which might exist in the liquid and on 
the surface of the wall of the flask. But as that infusion comes 
again into contact with the air, it becomes altered, as do all 

"Now suppose that I repeat this experiment, but that, before 
boiling the liquid, I draw out (with an enameler's lamp) the neck 
of the flask into a point, leaving, however, the tip open. This 
done, I bring the liquid in the flask to a boil, then I let it cool. 
Now, the liquid of this second flask will remain completely un- 
altered, not two days, not three, four, not a month, a year, but 
three or four years, for the experiment I am telling you about is 
already that long. The liquid remains perfectly limpid, as limpid 
as distilled water. What difference is there then between those 
two flasks? They contain the same liquid, they both contain air, 



both are open. Why then does this one become altered, while 
that one does not? Here, gentlemen, is the only difference be- 
tween the two flasks: In this, the grains of dust which are sus- 
pended in the air and their germs can fall through the neck of 
the flask and come in contact with the liquid, where they find 
appropriate aliment and develop. Thence, microscopic beings. 
In that, on the contrary, it is not possible, or at least it is ex- 
tremely difficult, unless the air is violently agitated, for the dust 
motes in suspension in the air to enter into the flask. Where do 
they go? They fall on its curved neck. When the air flows back 
into the flask, on account of the laws of diffusion and the varia- 
tions of temperature, the latter never being abrupt, the air enters 
slowly, sufficiently slowly for the dust and all the solid particles 
that it carries to fall at the opening of the neck, or to stop in 
the first part of the bend. 

"This experiment, gentlemen, is full of instruction. For notice 
well, that everything in the air, everything save the dust, can very 
readily enter the interior of the flask and make contact with the 
liquid. Imagine whatever you choose in the air, electricity, mag- 
netism, ozone, even things of which we are still ignorant, all can 
enter and come in contact with the infusion. There is only one 
thing which cannot enter easily, the dust suspended in the air, 
and the proof of that is, that if I shake the flask vigorously two 
or three times, in two or three days it will contain animalculae 
and molds. Why? Because the return of the air has taken place 
violently and has carried dust in with it. 

"And consequently, gentlemen, I too could say, showing you 
this liquid: I have taken my drop of water from the immensity 
of creation, and I have taken it full of nutrient jelly, that is, 
speaking scientifically, full of the elements appropriate for the 
development of inferior beings. And I wait, and I watch, and I 
question it, and I demand that it be willing to recommence for 
me the act of primitive creation; how beautiful a spectacle that 
would be! But it is mute, mute since these experiments were 
begun several years ago. Ah! that is because I have kept from it, 
still keep from it at this moment, the only thing it has not been 
given to man to produce, I have kept from it the germs which 
float in the air, I have kept from it life, for life is the germ, and 
the germ is life. Never will the doctrine of spontaneous genera- 
tion recover from the mortal blow which this simple experiment 
has given it." 

Pasteur then went on to recount how flasks containing infu- 


sion had the tips of their long necks fused in the flame of the 
torch after being boiled, and while still hot. When cool, the air 
within the flasks was, of course, at a low pressure, and upon 
breaking the tips, air would rush in until atmospheric pressure 
was reached. Of twenty such flasks opened on the Mer de Glace, 
only one became altered. Twenty opened at an elevation of 100 
meters in the Jura mountains yielded growth of microorganisms 
in five. Twenty opened at the foot of the same mountains showed 
growth in eight. As one approaches closer to the habitations of 
man, wherever dust is more abundant, the proportion of flasks 
showing contamination by germs increases. 

In concluding, Pasteur showed that even blood and urine, of 
all infusions believed the most putrescible, could be preserved 
for years in the state in which they are taken from the body, if 
kept from any exposure to air. "And note," he said, "that this is 
a case of liquids which have not been subjected to any rise in 
temperature. ... So, once more, the spontaneous generation of 
microscopic beings is a chimera." 33 


Some may be interested to know just how complex such a fun- 
damental substance as glutathione is. First discovered by Hop- 
kins in 1921, and shown to be a compound of cysteine (or cystine), 
glycine, and glutamic acid, its recent synthesis shows it to have 
the structural formula: 


O H H H O H-C-S-H H O 

H-O-C-C - G-C-C-N-G-G-N-G-C-O-H 



The presence of an R-SH substance in a cell may be deter- 
mined by the nitroprusside test. An excess of ammonium sulfate 
is ground with a little sodium nitroprusside, dissolved, and added 
to the tissue to be tested. Then a drop of strong ammonia is 
added. A brilliant purple color develops, its intensity varying 
with the concentration of the R-SH substance, and then slowly 

33 Oeuvres de Pasteur, Vol. 2, pp. 341-346- Masson et Cie., Paris, 1922. 


The Origin of Differences in 
Hereditary Patterns 

WE HAVE seen in Chapter I that mitosis brings about 
an exactly equal distribution of the genes, and that 
reproduction based solely upon mitotic cell division must 
result in genetic identity, accordingly limiting variation to 
the effects of the environment. Yet variety, well-nigh uni- 
versal among life-forms, is undoubtedly to a great extent 
genetic, as the differences between families show. Reproduc- 
tion among most organisms must then involve more than 
mere isolation of a reproductive cell formed through cell divi- 
sion. As we know, it does, usually being associated with sex. 


Sex is fundamentally the capacity to form certain sorts of 
reproductive cells, known as gametes. The essential feature 
of these cells is that they fuse to give rise to a new individual, 
thus differing from spores, which can begin development au- 
tonomously. The fusion of gametes is usually called fertili- 
zation, a word connoting an impetus to growth. The fusion 
has two consequences. One result, indicated by the word 
itself, is the removal of the block which normally prevents a 
gamete from resuming cell division. (We shall consider this 
aspect further in Chapter III.) The other is of great im- 
portance in bringing about hereditary variation: it is the 



aggregation within a single cell, and hence in the individ- 
ual developing from that cell, of genes derived from different 
parents. Since the impetus to growth and development can 
be provided by other means, we shall use the term syngamy 
for the fusion of gametes, in order to emphasize its heredi- 
tary consequences. The single cell, formed by the combina- 
tion of gametes from different parents, is called a zygote, 
from the Greek word for yoke. 

In simple organisms gametes are alike and are often in- 
distinguishable from other cells. However, among most or- 
ganisms there is a division of labor between the two gametes. 
One takes over the function of supplying the zygote with the 
necessary protoplasm, food, and cell structures. It attains 

A 3 CD 

Fig. 8. Progressive steps in the division of labor between male and female 
gametes, as seen in various gregarines (parasitic protozoans). A, gametes alike. 
B, gametes slightly different. C, gametes considerably different. D, gametes 
typically differentiated. 

a larger and larger size, consequently becoming less mobile, 
and is known as the megagamete, or ovum. This is the fe- 
male gamete. The other becomes especially fitted for loco- 
motion, and proportionally smaller and smaller. It is the 
male gamete, and is known as a micr o gamete , or sperm 
(spermatozoon). The differences between ovum and sperm 
have, no doubt, arisen in successive evolutionary steps. At 
least, a progressive series of such steps can be arranged from 
the types of gametes to be found in a number of groups of 
the simpler prants and animals, as, for example, among certain 
unicellular parasites (gregarines), which live in the body 
cavities of vertebrates (Fig. 8). 

In man, the gametes differ quite characteristically. If we 
look at the sperm, we find that it has a small oval head, flat- 


tened at the tip. The head of the sperm is formed from the 
highly condensed chromosomes of the nucleus with a little 
cap of granules from the cytoplasm. A short neck and a slen- 
der middle-piece come from the centrosome. A long delicate 
whiplike tail propels the sperm. This is produced by the 
elongation of the cytoplasm around a central filament, which 
grows out of one of the two centrioles, those minute granules 
at the core of the centrosome. So very tiny is the whole sperm 
that, according to calculation, all the sperms which will take 
part in the production of the next generation of mankind, 
some two billions of them, could be packed into a space half 
the volume of an aspirin tablet. (See Figs. 9$ and io^f.) 

The sperms of other animals are very similar, and the same 
parts can be identified in each (Fig. 10). In many instances the 
anterior cap is curiously modified, pointed, coiled, even hatchet- 
or corkscrew-shaped. 1 Among crabs and other Crustacea 
peculiar sperms are formed with a central body surrounded 
by radiating arms. Here the central region is the compact 
nucleus, the radiating arms are outgrowths of the neck, and 
a cylindrical or conical part opposite the nucleus is homol- 
ogous to the tail. The sperms of certain flatworms have two 
flagella instead of a single tail-filament. 

Plant sperms are also essentially similar. The motile types 
found in the lower plants usually have two whiplike flagella, 
like those of the flatworms just mentioned. Or they may 
have four or more, a step toward the situation in the ferns. 
Here the nucleus is coiled about the rounded cytoplasm, 
and the coil is continued by a structure from which delicate 
hairlike cilia stand out in tufts. This structure arises from a 
cytoplasmic body similar to that which forms the anterior 
cap of the head of animal sperms. The free-swimming sperms 
of the ferns and their allies are connected by transitional 
types with the nonmotile microgametes typical of seed plants. 
The ginkgo tree and the cycads, for instance, have simplified 

1 Beware of jumping at conclusions! These are probably not modifications 
for violently penetrating the egg. 



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Fig. 10. A variety of sperms. A, man. B, the field mouse Mils agrarius. C, 
the bird Chloris. D, the toad Bufo. E, the skate Raja (showing only a small 
portion of the tail filament). F, the liverwort Pellia. G, the crab Inachus. 
H, the seaweed Fucus. I, the water fern Marsilia. J, the cycad Zamia. (Re- 
drawn from Wilson's The Cell in Development and Heredity, after various 
sources. Courtesy of The Macmillan Company) 

conical sperms with a large nucleus and a spiral band of 
cilia about the upper region of the cell. These sperms, 
though motile, are carried within the tip of the pollen tube 
as it grows out from the pollen grain and are never set 
free. In cone-bearing evergreens (gymnosperms) such as the 
pine and fir, the sperm has no spiral band of cilia, and in 
some cases the cell boundaries and cytoplasm also break 


down, and the sperm is no more than a nucleus. This is 
the situation in all the flowering plants (angiosperms), the 
two microgametes in each pollen tube being simply nuclei. 

Thus we see that there are regular transitions from the 
sperms of man to the microgametes of the seed plants. Male 
gametes differ in particulars, but invariably have one feature 
in common— the nucleus. There are many sorts of adaptations, 
presumably for entering the egg; and there are various devices 
for securing motility; 2 but the one structure which is to 
enter the egg, and which must be propelled toward it, is 
certainly the nucleus. This is the one common feature of 
all microgametes. 

The megagamete, or ovum, is more like a typical cell. The 
animal ovum differs from that of the plant mainly in the 
presence of larger amounts of stored food, often of several 
kinds, and frequently of a number of complex envelopes, 
nutritive or protective. 3 Within the ostrich egg, for instance, 
the ovum is crammed with yolk, distending it to such an 
enormous size that it is the largest of all cells. Around this 
yolk is an envelope of albumen (the white of the egg), around 
that a tough white membrane, really double, and finally the 

2 It is worth noting that the means of locomotion used by sperms are 
identically those possessed by single-celled organisms. Nonflagellated sper- 
matozoa are either nonmotile or move slowly by cytoplasmic flowing. They 
thus resemble either the nonmotile sporozoans, diatoms, and desmids, or the 
rhizopods, such as the ameba and the radiolarians, with their flowing pseu- 
dopodia ranging from blunt, thick projections to long, delicate rays. Sperms 
with either one or two flagella resemble in their mode of locomotion the 
great group of flagellated unicellular organisms which lies in the borderland 
between distinctly animal and distinctly plant forms. The spermatozoa of 
toads and salamanders, with tails in the form of long undulating membranes, 
remind us of the trypanosomes. Finally, the ciliated sperms of the fern and 
cycad groups recall to us the thousands of ciliated infusorians, which often 
even have their cilia arranged in spiral rows like those of the cycad sperm. 
Without pressing resemblances too far, this is enough to show that isolated 
cells possess a few common means of locomotion: either by ameboid flowing 
and creeping, or by differentiation of vibratory cilia and flagella, or by an un- 
dulatory membrane. In discussing the course of differentiation in many- 
celled organisms, we shall find that their cells, too, employ the same devices. 
All life is united through these common potentialities of cell movement. 

3 An ovum surrounded by nutritive and protective coats is known in 
animals as an egg, in plants as an ovule. 


shell. The mammalian ovum is not as large as the eggs of 
other vertebrates. Surrounding it there is a layer of nutritive 
cells, the corona radiata, which is broken up and dispersed at 
the time of fertilization. The ovum itself is much smaller, 
130-140M in diameter, so that it is just visible to the naked 
eye as a small speck. It is roughly spherical, and contains a 
large nucleus, in diameter one third to one fourth that of 
the cell. The cytoplasm contains only a moderate amount of 
yolk (Fig. 9 A). 

These differences are clearly associated with later needs 
of the embryo. During the long period of incubation, a 
developing bird must rely entirely on the stores of food and 
moisture within the egg, and must be protected from injury. 
On the other hand, a mammalian embryo very rapidly 
establishes a source of supply through connection with the 
body of its mother and, warmly sheltered within the uterus, 
needs less in the way of protection. This also explains the 
situation in the megagametes of the seed plants. Food is 
stored up for the developing plant, though in the surround- 
ing layers and not in the ovum itself. Quite generally, then, 
stored food is present within ova, but its amount varies with 
that available elsewhere in the egg, and also with the length 
of the period during which the egg or ovule must depend 
entirely upon its own resources. 

Inasmuch as the substances making up the stored food 
not only furnish energy for growth and development but also 
supply the components of the living substance itself, they 
include inorganic salts, water, and proteins, fats, and carbo- 
hydrates. 4 

4 In the hen's egg, the composition of the yolk is approximately: 

Water 50% 

Fats, lipoids and sterols 35% 

Proteins 15% 

Inorganic salts 1 .5% 

(Na, K, Ca, Mg, Fe, Si, S0 4 , P0 4 , CI) 
Carbohydrates, except for a little free glucose, are lacking here, but in insect 
and mollusk eggs there is considerable glycogen. The relative absence of carbo- 
hydrates in eggs is what we might expect, for, in general, fats, which have 


The ovum always contains a nucleus and a surrounding 
body of cytoplasm. In the latter are often structures which 
are thus directly passed on to the zygote. Plastids, for ex- 
ample, which are concerned with photosynthesis or starch 
formation in plants, are transmitted in this way to the off- 
spring, and therefore stem entirely from the mother. In 
animal ova there are often pigment granules, and mitochon- 
dria and chondriosomes (granules and rods), which, there is 
evidence to believe, are seats of oxidative activity. Bacteria, 
filtrable viruses, and other parasites are also sometimes passed 
on in this way, as Pasteur found to be the case in the trans- 
mission of the "corpuscles" causing the fatal pebrine disease 
of silkworms. 

We pass now to the several phases in the process of fertili- 
zation, the interesting features of which can be considered 
briefly, especially since we shall confine ourselves mainly to 
the events found to occur in animals. How does a sperm find 
its way to %n egg? In one plant (Fucus) and perhaps in sea 
urchins, some substance secreted by the egg attracts sperms to 
it, but most attempts to demonstrate a chemical attraction 
between egg and sperm have been unsuccessful. Rather, the 
sperms seem to drive blindly about until they meet an ovum; 
or else, within a short time, they perish. In animals where 
fertilization is internal, there is, to be sure, a general guide 
in the nature of the passages traversed. 5 Ova which are fer- 

more potential energy per unit weight, are a better and more customary storage 
form than carbohydrates. The distribution of phosphorus in the yolk is espe- 
cially interesting because it differs materially from that in differentiated cells. 
In the yolk there is a high proportion of lecithin and a characteristic phospho- 
protein called vitellin; in tissues there is much less of these and the proportion 
of inorganic phosphates and of nucleoproteins is increased many fold. This in- 
dicates that in the cytoplasm the fats are used up to furnish energy, and that 
phosphorus-bearing proteins of a nutritive type, such as casein in milk, are 
broken down, transferred to the nucleus, and reconstructed in a form associated 
with chromosome activity. 

5 Sperms make their own way up through vagina and uterus, swimming 
purely at random. But the uterine tubes are lined with cilia which set up 
a strong downward current against which the sperms are helpless. The walls 
of the tubes, however, are greatly folded, and the folds are continually 
altering their contacts with one another, so that temporary compartments 


tilized in water often have a thick coat of protective jelly, 
which so increases their size that spermatozoa establish con- 
tact with them more readily. The mammalian ovum, as al- 
ready mentioned, has surrounding it a layer of nutritive cells, 
which similarly increases its size. 

Once a sperm meets an egg it appears to be entrapped, 
and so a large number of sperms are soon swarming about the 
egg. Wriggling vigorously, the sperms penetrate the outer 
coat of the egg. When this is a layer of cells, as in the mam- 
malian egg, it seems to be dispersed by their activity. Some 
ova, such as those of insects or fishes, have only one point at 
which they may be entered by a sperm; others, such as the 
mammalian ovum, can be entered anywhere. In either case, 
sperms reaching the surface of the ovum become passive. A 
small cone then bulges from the ovum toward one of the 
sperms, and it is drawn into the ovum, usually in entirety, 
but in some cases leaving its tail behind; or even, as in the 
worm, Nereis, leaving its midpiece too. Evidently neither tail 
nor midpiece can be considered essential to fertilization, but 
only the head— that is, the nucleus. 

Upon the entry of one sperm, fluid rapidly accumulates 
between the ovum and the toughening outer membrane of the 
egg. In eggs fertilized in water, this fluid is imbibed from the 
surroundings, but in mammals there is a very definite shrink- 
age of the ovum itself, which is thus so adapted that it de- 
pends upon its own supply of liquid. Every past change in the 
situation of the ovum, as of any cell, has necessitated certain 
corresponding changes in its own system. Or perhaps it 
would be better to say that changes in the genes controlling 
the cell system have made it possible for the cell to meet 
new situations more successfully! The instant result of the 

form and reform. In the center of each temporary compartment the current 
flows up, so that some sperms will be carried to the upper end of a compart- 
ment and into the next, as the folds alter the positions of their contacts. 
Chance thus determines not only which sperms reach the upper end of the 
uterus, but likewise which are first successful in concluding their journey on 
up the Fallopian tubes to the egg. 


changes just described is that all other sperms are prevented 
from obtaining entrance. Where the ovum is thus adjusted 
to the entrance of only a single sperm, poisons may cause the 
fertilization membrane to form so slowly that two or more 
sperms may enter. Development is always abnormal when 
this has occurred. 

The membrane, however, is not the only insurance that 
one sperm and no more will participate in syngamy. A sub- 
stance which diffuses out of mature ova, and which causes 
sperms swimming in water to clump together, ceases to be 
produced at fertilization or whenever the fertilization mem- 
brane is formed, whether by the action of the sperm or of vari- 
ous other agents (for example, butyric acid). The capacity of 
ova to be fertilized depends upon their content of this sub- 
stance, which has been named fertilizin. The instant a sperm 
enters an ovum, some sort of chemical reaction between 
sperm and fertilizin sets up a block to further fertilization. 

We next find the sperm turning right about immediately 
after its entry. Developing about the centrosome in the mid- 
piece, when this enters, there appears an aster. The centro- 
some divides and gradually there is formed a typical spindle. 
The course of events from this point on is determined largely 
by the stage of the egg nucleus. 

If the ovum is already mature (that is, if it has passed 

6 In eggs which contain a great deal of yolk (insects, amphibians, birds, 
etc.) more than one sperm normally enters; yet only one actually takes part 
in syngamy, and the remainder degenerate. Here the block set up by the 
reaction is not to sperm-entry, but to participation in that fusion of nuclei 
which is the essence of the whole series of events. This situation also pre- 
vails in most plants, but in flowering plants (angiosperms) a peculiar varia- 
tion is found. Here there are two microgametes, equivalent to sperms, in 
each pollen tube. Both penetrate the embryo sack, which contains, besides 
the megagamete and five cells destined to degenerate, two endosperm nuclei. 
One sperm unites with the megagamete, of course. The other, instead of 
disintegrating, as do supernumerary sperms in all animals and in the lower 
plants, fuses with the two endosperm nuclei, and the cell derivatives of the 
resulting triploid cell store up food for the developing embryo. This is the 
main foodstore in the seeds of monocotyledons, and since this group of 
plants includes all our cultivated grains, our principal food supply depends 
directly upon this double fertilization. 


through the process of meiosis, to be described in the next 
section), the nuclei of sperm and ovum approach each other 
and fuse. 7 The spindle grows, the fusion nucleus swells, and 
the chromosomes appear in it. The division which follows 
is typical. 

However, if the ovum is not yet mature, fusion with the 
sperm nucleus is delayed until maturation has taken place. 
In this event the sperm head, while waiting, imbibes fluid 
from the surrounding cytoplasm, and swells into a typical 
interphase nucleus. Next the chromosomes appear, and pass 
through typical prophase changes, so that by the time the 
egg nucleus is ready to participate the sperm's chromo- 
somes are ready to go on the spindle. The ovum's chromo- 
somes then usually occupy one half of the equatorial plane 
of the spindle, and the sperm's the other; and no real min- 
gling occurs until the daughter nuclei are reconstructed at 
the end of this cell division. The final result, however, is ob- 
viously the same as before. 

To sum up: the essential feature of syngamy is the com- 
bination in a new individual of hereditary factors (the genes, 
located in the chromosomes) as a rule derived equally from 
two parents. Other essentials for growth and development 
(protoplasm containing food and cell structures) may be, and 
generally are, contributed entirely by one parent. 

With one exception (see Chapter III, pp. 147-161), each 
gamete makes an equal genetic contribution to the offspring. 
For every chromosome contributed by the female parent in 
the ovum, a similar one is contributed by the male parent 
in the sperm, so that each chromosome possesses a "homo- 
logue." The genes in these homologous chromosomes must 
consequently be paired too and, while a gene may occasionally 
differ somewhat from its mate, in most cases they are un- 
doubtedly identical. Here one may well raise a question: 

7 That the two nuclei seen fusing in a fertilized egg are, respectively, those 
of egg and sperm and, hence, that the gametes are cells was demonstrated 
by O. Hertwig and by Fol, who were also among the six who determined 
the nature of cell division (pp. 12, 13). 


Is it true that our inheritance is always half maternal and 
half paternal? Where our parents do differ as to some trait, 
will we of necessity be a blend between them? Here is a 
family in which the mother is brown-eyed and the father 
blue-eyed, and every one of the children resembles the 
mother. What about that? Evidently syngamy alone cannot 
explain the facts. What additional factor is then involved 
in the transmission of the genes? 


Each act of syngamy provides a zygote with two sets of 
chromosomes, one from the egg, one from the sperm. Then 
if all the zygotes are to be supplied with no more than two 
sets of chromosomes, this number of chromosomes (the diploid 
number) must be reduced somewhere in the course of the life 
cycle to the number of chromosomes characteristic of the 
gamete (the haploid number). When and how? To grasp the 
full significance of this is in fact to master the basis of heredi- 
tary variability in sexual organisms. 

In animals, the halving of the chromosome number usu- 
ally takes place during the formation of the gametes, in two 
cell divisions which differ characteristically from ordinary 
mitosis and, together, are called meiosis. It may seem that all 
that should be necessary to halve the chromosome number 
would be the suppression of the duplication of the chromo- 
somes in some one mitosis. But we should not forget what 
was pointed out in Chapter I, that every gene (and hence 
every chromosome) is essential to the normal functioning 
of each cell. No merely random sorting of the chromosomes 
into two numerically equal groups could, therefore, provide 
complete sets of chromosomes as a regular occurrence. Ac- 
cordingly, we should expect some additional process to accom- 
pany the suppression of chromosome duplication, some proc- 
ess which would insure that each chromosome would be 


allotted to a different set from its homologue. Is this to be 
found in meiosis? 

As we observe prospective sex cells becoming mature, we 
can notice that they first become different from other un- 
specialized cells by passing through a prolonged period of 
growth, during which a large store of food is accumulated in 
the cytoplasm of each one. This is much greater in the 
potential eggs than in the cells which will produce sperms, 
but it is present in the latter, too. While this storage is going 
on, each chromosome, already doubled as usual for the next 
cell division, pairs up side by side with its homologue, so 
that there appear to be only half as many chromosomes as 
previously, while each one is clearly made up of four strands. 
(It is often called a tetrad while in this association.) This 
intimate pairing of homologous chromosomes, one of pater- 
nal and the other of maternal origin, 8 is known as synapsis. 
It endures for a considerable length of time, so that the 
prophase of this first division of meiosis is greatly prolonged. 
Later we shall see that synapsis affords an important oppor- 
tunity for the homologous chromosomes to exchange genes, 
but for the moment we shall notice only its effect upon the 
disjunction of the chromosomes. 

As the chromosomes become attached to the spindle, they 
are still paired. Separation then follows, not between the 
strands of each individual chromosome? but between the 
paired homologues. The two cells resulting from this divi- 
sion, therefore, each receive one chromosome from each pair, 
and thus get a complete set of already double chromosomes 
(see Fig. 11). In the second division, each chromosome is 
already double, and the usual duplication is suppressed. 

Meiosis thus requires two divisions, each of which dif- 

8 The demonstration that the chromosomes which pair are, respectively, of 
maternal and paternal origin is basic to the Chromosome Theory of Heredity, 
which has in turn formed the essential framework of modern genetics. It 
was made by T. H. Montgomery, University of Texas cytologist, in 1901, just 
after the rediscovery of Mendel's work. 

9 The term chromatid is used to designate a single strand of a split chromo- 
some or of homologous paired chromosomes. 



Meiotic Division I 

Synapsis of homologous chromosomes 
during prophase 

Fie n The two meiotic divisions. The original paternal chromosomes are 
shown shaded; the original maternal chromosomes in solid black. The diftei- 
ent pairs of chromosomes are distinguishable by their shapes and sizes, as 
corresponding maternal and paternal chromosomes are alike in these respects. 

fers from an ordinary mitosis. In the first division, there 
is the pairing and then the segregation of each chromosome 
and its homologue. In the second division, its initial phase, 
the duplication of the chromosomes, is inhibited. As a conse- 
quence, four cells, each with a haploid chromosome number, 
are produced from every potential reproductive cell which 
enters meiosis. How these haploid cells then become gametes 
will be related in Chapter III. 


We can now ask ourselves what benefit, if any, is conferred 
upon sexual organisms by the existence of syngamy and 
meiosis. What advantage does a diploid constitution ap- 
parently have over a haploid? This we can discern by con- 
sidering a certain ameba (Ameba diploidea) and some of the 
fungi (Ascomycetes, e. g., Pyronema). In the ameba, for 
example, two individuals conjugate, much as in the familiar 
process in Paramecium. A bridge of protoplasm is formed 
between them and, following meiosis, a haploid migratory 
nucleus from each crosses into the other, where a similar 
haploid nucleus has remained. When they separate, each 
individual therefore has two haploid nuclei, of different 
origin. Instead of fusing as they commonly do in other pro- 
tozoa, in this ameba these two haploid nuclei remain side by 
side, dividing synchronously. To all intents and purposes the 
essential function of syngamy, that of bringing together in 
one cell nuclear material of different origin, is therefore ful- 
filled. The ameba is diploid, and not haploid, through its 
life cycle. Yet when it prepares to conjugate again, the two 
nuclei first fuse, to be followed immediately by meiosis. 
This case— that of the fungus is essentially the same— is highly 
illuminating. It shows that the advantages of a diploid con- 
stitution, whatever they are, depend only on the presence 
within the cell of the two sets of chromosomes, although for 
meiosis to occur these must be in the same nucleus. 

Now just what feature of meiosis could occur only if the 
chromosomes of maternal and paternal origin are included 
in the same nucleus? Obviously, the pairing of the homol- 
ogous chromosomes— and, subsequently, their disjunction- 
could occur only if this were the case. Have we noticed all 
the consequences of this? If we glance at Fig. 1 1 again, we 
can see three pairs of chromosomes, one pair of big V's, one 
of medium-sized rods, and one of very small globules, shaded 
so as to distinguish those of the original paternal set from those 
of the original maternal set. But the sets of chromosomes 
sorted out into the gametes are not necessarily these same 


original sets; that is, the original paternal and maternal con- 
tributions are shuffled before they are redealt to sperms or 
eggs. Each gamete carries a complete set of chromosomes, 
for it gets one member of every pair, but without regard to 
whether they came originally from parental sperm or from 
parental egg. 

This shuffling results from the fact that each pair of 
chromosomes takes up its position on the spindle independ- 
ently of all the others. When disjunction occurs, A disjoins 
from a, its homologue, B from b, and so on. But A can go 
toward either pole, provided a goes to the opposite one; and 
B and C can also go toward either pole. Then A can go 
either to the same pole as B or to the opposite; so too it can 
go either with C, or opposite to it. In other words, the mem- 
bers of different pairs recombine at random, and all possible 
combinations will occur with equal frequency. There are 
eight of these, of which only two (ABC and abc) are the same 
as the parental combinations. The others are recombinations 
of the chromosomes, and hence of the genes in them. If we 
consider in addition a fourth pair of chromosomes, its two 
orientations on the spindle will make two combinations with 
each of the previous eight, that is, sixteen in all. But of these, 
again, only two will be the original parental combinations- 
the rest will be recombinations. 

These results may be summed up in a simple formula. 
Each pair can be oriented two ways; then 2 n gives the num- 
ber of combinations, where n is the number of chromosome 

2 pairs 2 2 = 4 combinations 

3 pairs 2 3 = 8 combinations 

4 pairs 2 4 = 16 combinations 

n pairs 2 n = number of combinations from n pairs 

For ourselves, with forty-eight chromosomes per cell (twenty- 
four pairs), the number of combinations is therefore 2 24 . Of 
all these (16,777,216), only two resemble the original parental 
combinations exactly. The chance of a human gamete re- 


peating either of these is therefore only one in 8,388,608. 
The odds indeed favor a new deal! 

We may carry this analysis a step further. Common con- 
ceptions of heredity trace one half of each person's character- 
istics to each parent. While this is not true, as we shall see 
later, it is a fact that each of us receives one half of our 
chromosomes from each parent. Can it be true, as com- 
mon ideas also conceive, that one fourth of one's heritage 
comes from each grandparent, one eighth from each great- 
grandparent, and so on back? Not in the least. There is 
one chance in 8,388,608 that not a single chromosome of 
ours was derived from a particular grandparent, and there 
is almost one chance in 300 that his contribution consists 
of no more than five chromosomes of the twenty-four in the 
set we receive from the parent on his side. For great-grand- 
parents the likelihood of proportionate contribution to any 
single descendant's heritage is even less; and of one's sixteen 
great-great-grandparents, there is better than an even chance 
that some one of them will not be represented in our heritage 
by a single chromosome. This takes us back only four gen- 
erations. With two more, we shall reach a generation in 
which we had more ancestors than chromosomes, so that we 
cannot possibly have inherited whole chromosomes from all 
of them. Now, as we shall find out later, there are more 
hereditary units than there are chromosomes, for chromo- 
somes do not always behave as indivisible units in transmis- 
sion (pp. 107-118). However, these hereditary units, the 
genes, are limited in number to probably not more than 
10,000 or 20,000, so that a mere five hundred years ago we 
must have had many an ancestor from whom we have failed 
to inherit so much as a single gene. 10 This news, however, 

10 i t should be pointed out that, wherever inbreeding has been extensive 
the number of ancestors is consequently less than *• at any nth generation! 
This would somewhat increase the chance of inheriting from each ancestor 
though not to any considerable extent in human stocks where extensive out- 
breeding is the rule. 


should be kept private, lest it greatly dishearten all those in- 
terested in genealogies and pedigrees. 

The number of possible combinations in the offspring of 
any pair is the product of the number of possible combina- 
tions in their sperms and eggs, that is, (2 n ) 2 . For us, this 
amounts to the staggering total of 281,474,976,710,656. It is 
easy to see why no two individuals produced from separate 
fertilizations ever chance to be identical. 

It is also interesting to reflect on the amazing odds against 
our ever being just the combination we turned out to be, 
with 281,474,976,710,655 chances to 1 against it. We are 
amazed when an acquaintance happens to win the grand prize 
in any such huge lottery as the Irish sweepstakes, but that 
chance is enormous compared with the inconceivable chance 
that we should be just what we are. 

Meiosis, then, has significance for heredity, not so much be- 
cause the chromosomes are reduced in number, as because in 
the process they are thoroughly reshuffled, and an almost 
limitless variety of new combinations of the hereditary factors 
results. In drawing these conclusions, to be sure, we have been 
making one important assumption— that every chromosome 
differs not only from all the chromosomes of every other 
pair, but also from its own homologue, in at least one respect. 
We should never obtain different hands (that is, recombina- 
tions) if our cards were all alike, no matter how much we 
shuffled them. As we estimate our hands according to the 
differences of the cards, so our knowledge of the hereditary 
pattern rests upon differences between genes, upon whatever 
differences there may be between the two members making 
up each pair. It is true that, for most pairs, the members are 
alike. Only occasionally do they differ. Yet all we can learn 
of the pattern directly, we must learn from those occasional 
differences between alleles. 11 

Now of the several possible states in which each gene can 

11 The two partners of any pair of genes are alleles (allelomorphs) of each 
other; in a broader sense, any genes which can become partners when 
brought together by syngamy are alleles. 


exist, not all are equally advantageous; some will be rela- 
tively deleterious. Since the genes are paired, any control over 
the processes of development exerted by a given gene is, to 
some extent, modified by its partner. If, then, one of the two is 
deleterious, the harmful effect is generally partly, and often 
even wholly, counteracted by its allele. The diploid consti- 
tution therefore provides insurance against any deleterious 
effects exerted by genes. On the other hand, a haploid cell 
carries only one gene of each sort, and there can be no 
counteraction of harmful effects if deleterious genes are 
present. Here the sinning gene has no good angel to atone 
for its evil action! 

This life and accident insurance is the great contribution 
of syngamy, over and above its contribution to individual 
variety. Yet we have answered one question only to raise an- 
other. We have now to look into the problem of the origin of 
varieties of alleles. 


Cell division begins with a duplication of each gene. As 
long as genes are derived from pre-existing genes, all repre- 
sentatives of any particular gene will therefore be alike. Nor 
is it possible to assume, as some early geneticists did, that all 
hereditary variation is simply the kaleidoscopic recombina- 
tion of original differences present in the progenitors of each 
species. This is not possible, because some genes are known 
to exist in a considerable number of different states, and we 
must accordingly either give up the postulate of a single 
origin or admit that genes, although regularly the most stable 
of living units, may occasionally alter. 

Variation, as we observe it, would be impossible were the 
genes immutable. While retaining their ability to duplicate 
themselves during mitosis, they must be able to mutate. Can 
this be observed— perhaps even produced artificially? 



Most of the unusual variations we see for the first time 
are not really new at all, but are reappearances of old traits 
which come to light through the recombinations of genes 
resulting from mating. The first true mutation to be re- 
corded in an animal appeared in a male lamb in the flock of 
Seth Wright, Massachusetts farmer, in 1791. This lamb had 
very short bowed legs, and from it was bred the Ancon sheep, 
a breed so short-legged they were unable to jump the low 

A 9i$0--- 


»40-'- ■-:-■■ --■■■■■? -^ 

v&k/ ' * '* - : '^ : - - • ' -" ' " ' V 

Fig. 12. An Ancon short-legged sheep beside a normal sister. (Courtesy of 
Department of Genetics, Agricultural Experiment Station, Storrs, Connecticut) 

stone walls around sheep pastures. The same mutation later 
appeared a second time, in Norway, after the early breed 
had become extinct (Fig. 12). Other examples of spontaneous 
mutation have been the appearance, in the Florida velvet 
bean, of a new variety able to flower and fruit anywhere in 
the south of the United States, instead of being limited to 
Florida and the Gulf region; and the appearance, in tobacco, 
of a new variety able to flower only when day and night are 
proportioned as in the subtropics, instead of as in Kentucky 
or Virginia, home of the parent variety. 


What are undoubtedly mutations have occurred in human 
populations, too, although we cannot be so precise as to the 
exact date. For example, there is a peculiar kind of woolly 
hair, oval in cross section instead of round like ordinary 
hair, and with thin places where it breaks easily. This makes 
it not only woolly but also "self-bobbing." (It is, however, 
not identical with the kinky hair of Negroes.) In 1786 there 
was born, of Norwegian farmer stock, a girl who had this 
woolly hair, and she has now had four generations of de- 
scendants, of whom many have had the same kind of hair. 
Whether the mutation first appeared in her, or in some ear- 
lier, unrecorded ancestor, we cannot say. The same trait, or 
one very like it, has been traced back for five generations in 
the little village of Rijnsburg, near Leiden, Holland; it has 
also turned up in our southern states. Perhaps these cases 
are of common origin, and the original mutation occurred 
many centuries ago. More likely, the mutation has occurred 
two or three times and maybe, in one of the cases, as recent 
as the eighteenth century. 

l^JThe scientific study of gene mutations began in 1910 in 
the laboratory of Thomas Hunt Morgan at Columbia Uni- 
versity. One day, among the hundreds of ordinary red-eyed 
fruit flies in a culture bottle, a single male fly with white 
eyes was discovered. From this mutant fly a race of white- 
eyed flies was bred, and by crosses with the normal red-eyed 
flies the hereditary behavior of the new gene was deter- 
mined. The great search was on! During the next seventeen 
years more than 15,000,000 flies, mainly from purebred stocks 
known to be free from mutations, were scrutinized for new 
forms. In this way about 500 mutations were found. There 
were flies with altered eye color— pink, brown, sepia, purple, 
orange, and many other shades; there were flies with the 
regular rows of eye facets disarranged, with the size of the 
eye diminished; there were even flies with no eyes at all. 
There were types with wings bent or curved, held out- 
stretched from the body, blistered, scalloped, nicked, short- 



ened, or entirely gone— poor creatures able only to hop or 
crawl about. Others were Negroid races, or "Nordics," of a 
light yellow body color instead of the ordinary gray. Still 
others had bristles appearing snipped off, or close-shaven. 
And in one mutation the antennae on the head were actu- 
ally replaced by what looked like legs! Many of these changes, 
of course, were so drastic that the mutant individuals were 
feeble, dying young, unable long to survive the competition 
of normal flies bred in the same bottle. 

All this might lead us to think that Drosophila is especially 
subject to mutations of its genes. But when we recall that 
almost a score of millions of flies were examined to find these 
500 mutants, the fruit fly does not seem so very mutable after 
all. On the contrary, most genes are extremely stable. Al- 
though their individual mutation rates vary considerably, 
with few exceptions all the rates are extremely low. 

Not all mutations, of course, produce changes in the organ- 
ism visible to an observer looking only upon the exterior. 12 
Many morphological changes will be entirely internal, and 
these will very likely be of even greater importance to the 
animal or plant than superficial, readily observed changes. 
Moreover, structure is but a means to function and is itself a 
product of function-the creation of physiological processes. 
Mutations that alter structure must do so by altering these 
processes. Other changes in physiology may be unaccom- 
panied by changes in visible structure. To estimate their 
frequency we can look for alterations in "viability" and 
"fertility." If we compare the proportion of flies of one type 
which successfully emerge as adults with the proportion of 
some standard type hatching in the same culture, 13 and if 

12 One reason the fruit fly has been so favorable an object for genetic study is 
that since, like all arthropods, it has an external skeleton, the proportion of 
mutations with externally visible effects is higher than in forms like vertebrates, 
which have a relatively undifferentiated exterior. 

is This point is essential. If environmental factors were not identical for our 
two types, differences might be attributed to them rather than to genetic 
make-up. In scientific experiments all factors except the one whose effects are 
being tested must be kept constant. 


any difference between the types is inherited, we can speak 
of a genetic difference in "viability." If we compare the 
frequency of hatching eggs from matings of two types of males 
with the same females, or from two types of females mated 
with the same males, we can similarly measure any genetic 
difference in "fertility." If we have started with types of 
known viability or fertility, and then we detect an inherited 
difference in these respects in the course of further breeding, 
we can attribute it to a mutation. 

In the completest analysis of this sort yet made, it was 
found that mutations which lower the viability somewhat 
(up to 15 per cent), but do not produce any externally visible 
effect, form the most abundant group, making up almost two 
thirds of the total. They are about twice as frequent as those 
mutations which reduce the viability so much (70 per cent or 
more) that they usually cause death. These are called lethals 
or semilethals. They sometimes involve visible deformities, 
but often, in the occasional individuals which do survive, 
have no obvious external effect. The mutations which 
markedly alter the appearance practically always have a some- 
what reduced viability, too. They are extremely infrequent, 
however, as compared with the other two groups, being at 
most 1/25 as common as the lethals. As for beneficial mu- 
tants, the y are the rarest of all, scarcely amounting to so much 
as one third of 1 per cent of all mutations; only one turned 
up among 356 mutations in this experiment. Most mutations 

_in the fruit fly, we can conclude, produce no visible external 
change and are deleterious. 

Turning to mammalian heredity, we can find plenty of 
mutants of definitely deleterious effect, many that are lethal. 
The generalization just made is by no means limited to fruit 

_flies! Many such mutants, for instance, have been described 
in cattle, chiefly those which kill the calves late in prenatal 
development or shortly after birth; for these are most readily 
detected. The "parrot-beaked" calf has an abnormal lower 
jaw with impacted molar teeth, a condition resulting in death 


a few hours after birth. "Amputated" calves have neither 
limbs nor lower jaw; they are born dead. "Elk-calves," on the 
other hand, have normal legs and jaws, but an extremely 
shortened spine and trunk; these, too, are stillborn. "Bull- 
dog" calves (Fig. 13) have extremely short legs, a dumpy build 
and scooped-out faces like those of human achondroplastic 
dwarfs; they are known in two forms: one always stillborn, 

Fig. 13. A "bulldog" calf from the Norwegian Telemark breed. The malfor- 
mation of its spinal column and legs is due to a recessive lethal gene. (From 
Mohr's Heredity and Disease. Courtesy of W. W. Norton & Co.) 

the other (less extreme) managing to live a few days. These 
by no means exhaust the list. 

In man there are many similar examples, ranging all the 
way from conditions lethal before birth to those only mildly 
disadvantageous. Extreme lethals include certain malforma- 
tions of skin, limbs and jaw, and brain-case (Fig. 14). Lethal 
during relatively advanced development are such hereditary 
degenerative diseases as Wilson's disease and Huntington's 
chorea, a form of "St. Vitus's dance." Detrimental, but not 
necessarily lethal, are congenital absence of hands and feet 
(Fig. 15), hemophilia, harelip and cleft palate, and numerous 
other genetic conditions. Finally, some mutants, such as 
Polydactyly or the woolly hair mentioned earlier, are not 
obviously detrimental. 14 Other genes may even be advanta- 

14 There is a discussion of representative hereditary diseases and lethal 
conditions in man in O. L. Mohr, Heredity and Disease, Chap. IV, Sec. 1-3 
(W. W. Norton, New York, 1934). The medical terminology lends a false ap- 



geous. In the tropics those that 
produce quantities of melanin 
(black pigment) in the skin would 
probably be so. But, of course, we 
have no measure of the frequency 
of these different sorts of mutation 
in man. We must turn to Drosoph- 
ilaior that. 

[Even in Drosophila we would 
know little of mutation rate, espe- 
cially of the different categories of 
effects, were it not for the dis- 
covery by H. J. Muller in 1927, at 
the University of Texas, that muta- 
tions can be induced at a high rate 
by subjecting the genes to x-ray 
bombardment. Treatment, within 
such limits of severity as flies can 
stand, will raise the mutation rate 
from the low spontaneous level 
previously described to two or 
three mutations per individual! 
This is an increase of about one hundred fold! At the same 
time, the genes go on mutating in the same respective propor- 
tions, without any differential effect of the treatment. Hence, 
it is practicable to make comparisons of the different sorts of 
mutation (advantageous, slightly detrimental, semilethal, and 
lethal), and the experiments on viability just described made 
use of this technique. 

The use of radiation to increase the mutation rate has 
yielded nearly all our information about mutation, and from 
the study of mutation we have learned much of what we 
know about the nature of the gene. We will not go into the 

Fig. 14. "Amputated" abor- 
tion. The parents were first 
cousins. (From Mohr's He- 
redity and Disease. Courtesy 
of W. W. Norton & Co.) 

pearance of difficulty to the discussion. See also Heredity in Man by R. R. 
Gates (Macmillan, New York, 1931) and the graphic popular presentation, 
You and Heredity, by A. Scheinfeld (Stokes, New York, 1939). 



nature and cause of the mutation process here, for we are con- 
cerned mainly with the nature of the gene as it bears upon the 
processes of development. We will therefore summarize briefly 

Fig. 15. A dominant mutation resulting in the congenital absence of hands 
and feet. The mother of the family is normal, but her husband, like his 
three children and brother in the picture, lacked hands and feet. (Courtesy 
of O. L. Mohr) 

what has been learned about the gene through the study of 

We have already seen (1) that most genes are extremely 
stable; (2) that mutants are frequently devoid of visible effect; 
(3) that most mutations are, to a greater or less degree, dele- 
terious. To these we may add: 

(4) Mutations may occur at any time in the life cycle. 
Mutations are not limited to reproductive cells, but may- 
occur in somatic tissue, making mutant areas of a size corre- 
sponding to the number of descendant cells produced. Evi- 
dence that the physiological state of the cell affects the muta- 


tion rate is still inadequate, but it is possible that this may 
turn out to be of very great importance. 

Jg\ A mutation of a gene may consist of either its loss, its 
.change, 9LJiJ:9IL.9L change, of its neighbors. The first is 
known from the fact that many lethal genes in the fruit fly 
can be shown, by cytological observation of the giant salivary 
gland chromosomes, to involve actual deficiencies of small 
parts of the chromosome. The second can be shown indi- 
rectly by cytological study, too, through an absence of any 
detectable loss or rearrangement within a giant chromosome 
carrying a mutation, but is shown more convincingly by the 
ability of many visible mutants to mutate back to their orig- 
inal states. The third is shown by the fact that certain genes, 
even though they experience neither loss nor change them- 
selves, mutate when they are removed from one neighbor- 
hood and brought into juxtaposition with new neighbor 
genes. All this is extremely important, for we detect genes 
by their differences from their alleles, and these differences 
have arisen by mutation. Since mutation includes several 
phenomena, it is illogical to assert that we consistently mean 
any one thing at present by the term gene. 15 

(6) A given gene may become altered in more than one 
way. This goes further than the preceding conclusion, as it 
refers to the multiple variety of those reversible changes 
which are neither losses nor "position effects." Here we mean 
that a particular gene may have more than one sort of allele, 
and that the effects of these alleles may vary quantitatively or 
qualitatively. The number of possible changes varies with 
each gene, so that series of such "multiple alleles" run to 
different lengths. The number of alternative combinations 
involving one or another allele of such a multiple series adds 
enormously to the possible variety of the hereditary pattern, 
and will be discussed in the next section. 

is This is often misunderstood. In theory we often define a gene as a unit 
in the chromosome. In practice we always identify a gene by its effects, 
hence, confusion. 


Hereditary variation is primarily due to these alterations 
of the genes. Their appearance in various combinations— in 
other words, the emergence of various sorts of individuals- 
is, however, due to the mechanism of syngamy and meiosis. 
We have now to see how the pattern is made up. J 




We have found that the significance of meiosis for heredity 
lies in the recombination of the hereditary factors, the genes, 
which it brings about. Syngamy makes the variety of possible 
combinations vastly greater. From the chance shufflings of 
the chromosomes in reduction and the random mating of 
gametes, each of us emerged as one of 281,474,976,710,656 
possible types our parents could have produced, a number 
that is more than 100,000 times the present population of 
the earth. 

It is mentally impossible to follow such permutations as 
these. No wonder many a biologist of the nineteenth cen- 
tury felt that the nature of heredity was doomed to remain 
an insoluble perplexity! But after all, we do not need to 
know the course of each thread to understand how a great 
tapestry is woven. The pattern of heredity can be readily 
comprehended by tracing no more than two or three of the 
"threads" which make it up. It was Mendel who showed us 
this truth. The work of Mendel, at first completely ignored, 
has become in our present century the foundation of the 
tremendously increased knowledge of heredity that man now 
possesses. 16 

i6Gregor Johann Mendel, born in Silesia in 1822, was the son of a peasant 
farmer whose study of fruit-tree grafting engendered the first interest in 
genetics in his young son. Mendel's education involved great sacrifice by his 
family, a younger sister even giving up part of her dowry that he might 
finish the Gymnasium (high school). On graduating, he entered the Augus- 
tinian monastery at Briinn, probably as a result of the influence of a 


Mendel was clear-sighted enough to see that it was hopeless 
to try to work out all the intricacies of heredity at once. He 
determined to test the inheritance of no more than a single 
pair of contrasting characters at a time. Working with 
garden peas, he selected such alternative traits as tallness versus 
dwarfness, red flower color versus white flower color, green 
versus yellow seeds, smooth versus wrinkled seeds, and so 
on, for different tests. Instead of restating his results, which 
can better be gotten direct from his own paper, we shall 
take a human trait as our example, it having been well 
established by now that practically all hereditary traits are 
handed down in the same fashion. 

Probably all of us have heard of albinos, people with a 
complete lack of pigment in the skin and outer layer of the 
body, including the eyes. They are a dead-white, hair and 
skin, and have eyes that appear pink, since, with no pigment 

teacher who was a monk of that order. He attended the University of 
Vienna for two years, at the expense of the monastery, and then returned 
to Brunn to teach physics. While making a reputation as a good teacher, he 
carried on his famous plant-breeding experiments. After eight years the 
experiments with peas were completed, and in 1866 he communicated them 
to the Society at Brunn, where they aroused little remark. Three years later 
the paper on hawkweed (Hieracium) hybrids suffered the same fate. Copies 
which were sent to Nageli, the leading geneticist of the time, were treated 
no better. Despondency ensued, and Mendel published no more. The results 
of his vast experimentation with bees seem forever lost to us, as even the 
notes have disappeared. Elected prelate of the monastery in 1868, he became 
embroiled with the Austrian government over religious taxation, advocated 
"passive resistance," and resisted to the last. "From being a cheerful, friendly 
man," says William Bateson, "he became suspicious and misanthropic." The 
last ten years of his life were passed in disappointment and bitterness. Often 
he said, "Meine Zeit wird schon kommen" (My time is coming). Sixteen 
years after his death in 1884, his day did come, when three great breeders, 
Correns, deVries, and von Tschermak, simultaneously confirmed his results, 
and published to the world his enduring fame. 

There is a good full-length Life of Mendel, by Hugo litis (W. W. Norton, 
New York, 1932). There is also an excellent biographical sketch of Mendel by 
William Bateson, the English geneticist, in Mendel's Principles of Heredity, 
together with portraits made in 1862 and 1880, and full translations of the pa- 
pers on peas and hawkweeds. (Cambridge University Press, 1909.) The paper 
on peas should be read by all persons interested in genetics. It is a masterpiece 
of scientific writing describing a masterpiece of scientific experimentation. 


in the iris, the red of the blood in the numerous fine blood 
vessels of the eye shows up. 

Albinism is found in practically all vertebrates. We have 
all seen white rabbits, rats, and mice that have pink eyes; 
but albino deer, squirrels, weasels, porcupines, alligators, 
rattlesnakes, frogs, fish, and numerous birds, such as peacock, 
turkey, crow, robin, and sparrow, also occur. Literature, too, 
presents the classic example of "Moby Dick," the albino 
whale. In all these forms it seems probable that the trait 
is due to the same gene. In other words, this is one of the 
genes we share with lower forms of life, a reminder that 
not all genes possessed by man are "human" genes. 

Let us, then, breed a pair of mice, one of them of the ordi- 
nary wild gray type, the other a "white" (albino). When their 
first litter is born, we discover that all the offspring are like 
the gray parent— and no matter how many such crosses we 
make and how many litters we raise, this is the only kind 
we shall ever obtain, barring mutation. All the first genera- 
tion (¥ x ) are uniformly gray. 

Now if we mate these gray (nonalbino) mice of the F x to- 
gether, what will we get? Some of the litters will contain 
white mice! And if we raise several dozen such litters, and 
notice how many of each kind there are in all, we shall find 
that there are about three times as many gray (nonalbino) 
mice as albino ones. And the more such litters we raise, the 
more exactly will we find that this ratio of 3 : 1 is obtained. 
How can we explain it? 

To begin with, it is evident that the albino trait has reap- 
peared after "skipping a generation," so that whatever factor 
is responsible for it must have been carried by the gray mice 
of the first generation of offspring, along with the factor re- 
sponsible for their grayness. One of these factors must domi- 
nate the other, so that, although both are present, only one, 
the dominant, is expressed, while the other is recessive. 

These factors we now call genes. Since, as we recall, sperm 
and egg each contribute a set of these genes to the individual 


through syngamy, and consequently every gene in one set has 
a partner, or allele, in the other set, we may represent those 
concerned here by a pair of symbols, A for the dominant 
(nonalbinism), a for the recessive (albinism). 17 If we started 
with gray and albino mice of pure stock, their genotype 
(genetic constitution) was A /A and a/a. What happens to 
these pairs of genes at meiosis? The homologous chromo- 
somes, and hence the genes within them, first pair and then 
disjoin. In the gametes of one parent, then, A will have dis- 
joined from A, and every gamete will carry A. In the other 
parent a will disjoin from a, and every gamete will carry a. 
We may diagram this as follows: 

A/A a/a parental genotypes 

Meiosis I \ 

a a gametes 

There is only one sort of ovum here, and only one sort of 
sperm. Hence, at syngamy, an ovum carrying A is necessarily 
fertilized by a sperm carrying a; and the resultant zygote is 
A /a. Finishing our diagram: 


genotype of zygote 

17 At this time it will be well to become acquainted with the essentials 
of the geneticists' symbolism, which we shall need to use repeatedly. Letters 
are used to represent individual genes, with the dominant allele capitalized 
and the recessive a small letter; or the mutant allele is given a letter symbol, 
and the "normal," i.e., wild type, allele has the same symbol with a "+" 
superscript. Thus A and a are dominant and recessive alleles, or a+ might 
be used for A, since here the dominant is the normal allele. A dominant 
mutant, such as Bar (p. 110), has the symbol B, and its recessive wild-type 
allele is B+. Since alleles are carried in homologous chromosomes, a geno- 
type is written with one bar (or two) between the alleles, e. g., A/a, 
A A 

T . or =. 

8 4 


The genotype of the zygote is not like that of either parent, 
for the two genes of the pair we are following are now un- 
like. The zygote is hybrid, not pure; or, to use the conven- 
ient terms of the geneticist, the parents were homozygous, 
but the offspring is heterozygous. We should note another 
fact about the offspring of this mating. Since the only com- 
bination of gametes is A with a, all the offspring, no matter 
how many, will have the genotype A /a. They will all be 
heterozygous! And they will all be alike! Or to generalize, 
we can say that when parents differ with respect to some trait 
for which each is pure (homozygous), their offspring are all 
heterozygous and uniform. In the present case, since A 
dominates over a, the heterozygous A /a offspring will be uni- 
formly nonalbino, and experience shows that this is really so. 
But even where there is no dominance, as we shall see, the 
rule holds true. 

Now see what happens when two such heterozygous indi- 
viduals mate! First-meiosis; then-syngamy: 


parental genotypes 


This time, when we come to syngamy, we can see that 
there are a number of possible combinations. We can best 
keep these straight by using the so-called checkerboard 
method, listing the gametes of each parent along one side, 
and filling the squares with the appropriate combinations: 










Result: Three different genotypes, in the ratio 1 A/A : 2 A/a 
: 1 a/a. The offspring of heterozygous parents comprise two 
heterozygotes to one of each homozygous type. Since A is 
dominant, the heterozygotes here will be nonalbino, resem- 
bling the homozygote A /A, so that there will be three non- 
albinos for each albino. This 3 : 1 ratio is the phenotypic 

Fig. 16. Albinism in man. Normal parents with three albino children and 
four normal. (Courtesy of O. L. Mohr) 

ratio. It states the relative frequencies of the offspring when 
classed by their traits as expressed. However, when we come 
to predict the results of various sorts of mating, it is always 
the genotypic ratio that must be made the basis of our analysis. 
The family shown in Fig. 16 illustrates what we have been 
saying. "As seen from the picture both parents are perfectly 
normal. That they nevertheless carry the recessive gene is 
evidenced by their offspring. This fundamental relation, 
that a strictly hereditary anomaly may be transmitted through 


perfectly normal individuals, has been the cause of much 
misunderstanding. And still many people stick to the en- 
tirely wrong conception that only those anomalies are hered- 
itary which manifest themselves both in parents and in off- 
spring. Nothing could be more erroneous. 18 

Have the A and a genes been altered in any way by their 
association throughout the parental generation? Not at all! 
The A/A and a/a offspring are like their grandparents^ The 
a/a offspring are just as pure albino as the original strain be- 
fore hybridization and, as our next example shows, breed as 
true. If we mate A/A with A/A and a/a with a /a, each cross 
yields only one possible type: 

(0 ( 2 ) 

A/A X A/A a/a X a/a 

I \ / \ Meiosis 

A A A A ; 

A/A a/ a 

Result: Matings between similar homozygotes yield only 
homozygotes of the parental type. 

If we look back at the cross between two heterozygotes, we 
are reminded that one fourth of the offspring are homo- 
zygous A/A and one fourth are a/a. The crosses just dia- 
gramed thus indicate what results we can expect if an indi- 
vidual of either of these homozygous groups is mated with its 
like. One half of the offspring of the A/a by A/a cross will 
give rise, upon mating with their like, to pure lines, A/A and 
a/a. The other one half, heterozygous like their parents, will, 
when bred within their own group, naturally repeat the same 
ratio in their offspring, 3 nonalbino : 1 albino-or by geno- 

Mohr, O. L. Heredity and Disease, pp. 64-65. W. W. Norton, New York, 





types, 1 homozygous nonalbino : 2 heterozygous nonalbino : 1 
(homozygous) albino. The results thus far are summed up in 
Fig. 17. These parallel the fundamental facts found by Men- 
del in his crosses with peas, using seven different pairs of con- 
trasted characters. His results led to the conclusion that in- 
herited characters are due to units which are paired in the 
organism but segregate in the formation of the gametes, 
the latter therefore being pure. The factors have not been 
affected by their association. This is the first, and most im- 
portant, Mendelian law of inheritance. 

We can make one other type of cross involving these genes. 
The heterozygous type can be mated with either homozygous 


A/A X A/a 

M M 



a/a X A/a 
a a A a gametes 

A/A A/a 

A/a a/a 

Sy n gamy 

The cross A/ A by A /a gives us the ratio 1 A/A : \ A/a, that 
is, one homozygous dominant to one heterozygote; pheno- 
typically all will be nonalbino. The cross a/a by A/a, on the 
other hand, gives us 1 A/a \ 1 a /a, that is, one homozygous 
recessive to one heterozygote; or, half nonalbino and half 

When can a purely recessive trait, such as albinism, show 
up? Obviously, from our diagrams, only when both parents 
carry the gene for it. Then, should the parents both be 
heterozygous, it will show up in one fourth of the children. 
This explains why "consanguineous marriages favor the ap- 
pearance of recessive traits." 21 Closely related people, since 

21 Mohr, op. cit., p. 26. 



fs &§*&& mimimirii &mlmiQ§ oktlak^ 

Fig. 17. Cross of a purebred colored rabbit with an albino rabbit. F^ first 
generation, all offspring colored. F 2 , second generation, colored and albino 
rabbits in the ratio 3 : 1'. F 3 , third generation, pure colored, segregating, and 
pure albino families in the ratio 1:2:1. (Redrawn from Mohr's Heredity 
and Disease. Courtesy of W. W. Norton & Co.) 

they have received from their common ancestry at least some 
of the same genes, are much more likely to possess common 
recessives than unrelated people. This appears clearly in the 
pedigree for albinism shown in Fig. 18 (p. 91). The uncle- 
niece marriage (A), which resulted in four albinos among six 
children, shows that the uncle must also have carried the al- 
bino gene. The first-cousin marriage (B) also showed, by the 
production of an albino child, that the parents carried this 
gene in common. 

With these principles in mind, let us next compare with 
the crosses involving albinism some similar crosses in which 
neither of the two alleles is dominant, but in which the pheno- 
type results from their approximately equal effectiveness. 
And to remind ourselves that the phenomena of meiosis and 
syngamy are essentially similar in all organisms, let us select 
an example from a plant— a seed plant. 

There are both red- and white-flowered four-o'clocks (Mira- 
bilis jalapa). The cross red by red gives only red-flowered 
offspring; white by white gives only white-flowered plants. 



These two types are homozygous. When a red flower is 
crossed with a white one, all the first generation (F x ) are pink; 
and if we cross together two pink flowers, we get 1 red : 2 
pink : 1 white, in the second generation (F 2 ). Evidently the 
genes determining this difference in color are alleles (R and r). 
When we diagram these crosses, however, they turn out to be 
just like the albino case. 

parental genotypes 
F x genotype 








1 R/R : 2 R/r : 1 r/r 

The genotypic ratio is still two heterozygotes to one of 
each of the homozygotes, as before. The phenotypic ratio is, 
however, not 3 : 1, but 1 red : 2 pink : 1 white. Thus we 
learn that the genotypic ratio, which depends solely upon the 
nature of meiosis and syngamy, is constant for a given type of 
cross, while the phenotypic ratio depends upon the relative 
dominance of the alleles and varies with this from case to case. 
The blending of red and white in the hybrid only serves to 
emphasize even more strikingly the fundamental independ- 
ence and aloofness of the alleles. For it is clear that "the genes 
themselves neither blend nor contaminate one another. When 



reduction brings the time for parting, each goes its solitary 
way, bearing no trace of having been associated for months or 
years with the other within the microscopic chambers of the 
cells. Moreover, it evidently makes no difference whether 
we use a red-flowered plant for our original male parent and 
a white for our female, or vice versa. In both cases the hy- 
brids will be pink. All that matters is the kind of genes in 
the resulting mixture." 20 

One more example from the four-o'clock, this time a cross 
between a heterozygote and a pure white: 



R i 




parental genotypes 








Genotypic ratio i R/r : 1 r/r 
Phenotypic ratio 1 pink : 1 white 

This is the same result we obtained for the corresponding 
cross of heterozygous nonalbino with albino, and as before, 
the phenotypic ratio indicates precisely the proportions of 
the types of gametes formed by the heterozygous parent. 
Such a cross, known as a backcross, is for this reason of great 
practical value, since it enables us to determine the frequen- 
cies of the various types of gametes an individual produces. 
By backcrossing to the homozygous recessive type-in the 
absence of dominance either homozygote would do-we may 
discover the hidden genotype which is of such ultimate 

20 Wells, H. G., Huxley, J., and Wells, G. P. The Science of Life, Chap. I, 
pp. 479-80. Doubleday, Doran, New York, 1931. 


9 1 



TCQfOOjO o Oft ##tt #ft 

Fig. 18. A pedigree illustrating the recessive inheritance of albinism in man 
through four generations (I-IV). At A, a marriage of a heterozygous uncle 
with an albinotic niece; a backcross. At B, a marriage of heterozygous first 
cousins. ('After Tertsch) 

In the Andalusian fowl there is another sort of blending, 
one which results in a distinctly new type. Black and 
splashed-white are homozygous, and when crossed blend to 
produce the highly regarded "Blue Andalusians." Since 
these are heterozygotes, like the pink four-o'clocks or the 
heterozygous nonalbinos, when interbred one fourth of their 
offspring are of one homozygous type (black), and another 
one fourth are of the other (splashed-white). Imagine the 
chagrin of the fancy breeder trying to get a line of Andalusian 
blues that would breed true! 

Another common sort of blending involves lethal genes. 
Dexter cattle are relatively short-legged but otherwise nor- 
mal. However, they do not breed true but, like the Anda- 
lusian blue fowls, show the marks of heterozygosity. Dexter 
bull crossed by Dexter cow gives one fourth normal, one half 
Dexter, and one fourth "bulldog" calves. The latter, as de- 
scribed in the last section (Fig. 13), are stillborn or die 
shortly after birth. The short-leggedness of Dexter cattle is 



therefore a blend of the effects of the lethal gene and its nor- 
mal allele. 

Lethals that are completely recessive are very abundant. 
They can be detected by the change in the expected ratios. 
If L is the normal allele, and / the lethal, the cross L/l X L/l, 
instead of producing 3 dominant to 1 recessive, will appar- 
ently produce only dominant offspring, as the recessives die 
off during development. Dominant lethal mutations presum- 
ably occur, too, but as they kill every individual carrying 
them at once, they cannot be inherited. 

Earlier we noticed that a gene is not limited to two states 
(p. 79). While in man only two alleles of the albino gene are 
known, in mice there are four, in rabbits six, and in guinea 
pigs five. In Drosophila there is one series, affecting eye 
color, which numbers no less than thirteen alleles that can be 
distinguished from one another. However, inasmuch as 
every diploid cell carries its genes in pairs, not more than 
two members of any such series of multiple alleles can be 
present at one time. The crosses "albino by nonalbino" and 
"red- by white-flowered four-o'clock" therefore serve equally 
well as examples for crosses involving multiple alleles. The 
only additional factor to be taken into account is the domi- 
nance of the alleles. This can be discerned at once from the 
phenotype of the offspring of a cross between homozygotes. 

Take, for example, the albino series in rabbits. One allele 
produces, when homozygous, a form known as the Hima- 
layan albino, which has black extremities— feet, ears, tail, tip 
of nose (Fig. 19). Cross a homozygous Himalayan albino 
(c h /c h ) with a pure full-color (C/C), and the hybrids (C/c h j 
are all full-color. The gene for Himalayan albinism is, there- 
fore, recessive to that for full-color. But cross the same Hima- 
layan albino with a full albino (c a /c a ), and all the offspring 
(c h /c a ) are Himalayan albinos. The gene for Himalayan al- 
binism must be dominant to that for complete albinism. The 
same gene can be both dominant and recessive, depend- 
ing upon which allele it is compared with. Dominance is 



purely relative. Still another allele of this series is shown in 
the illustration. This is chinchilla (c ch ), which has no yellow 
in the fur, and is consequently a silvery gray, highly prized 
by furriers. Chinchilla is dominant to both Himalayan and 
albino, but is recessive to full-color, so that the series, in 
order of dominance, runs as follows: C> c ch >c h >c". 

Fig. 19. The albino series of multiple alleles in rabbits. Upper left, full- 
color; upper right, chinchilla; lower left, Himalayan; lower right, albino. 
(From Snyder's The Principles of Heredity. Courtesy of D. C. Heath and 

The relation between any two alleles of such a multiple 
series could, of course, also lack dominance (perfect blend- 
ing), or dominance might be incomplete. An interesting 
combination of several such relationships is to be found in 
man. The best known multiple allelic series in human be- 
ings consists of three members which determine the blood 
groups. To understand the nature of these we must digress 
a little. 

Foreign proteins (antigens) injected into the circulation of 
an animal stimulate the cells of the animal to produce char- 
acteristic antibodies which will react with their antigens and 
neutralize their effects. When observed outside the body, 


this reaction frequently takes the appearance of a clumping, 
or agglutination, of the antigen. 

In 1900 Dr. Karl Landsteiner, then in Vienna, 21 discov- 
ered that the red blood cells of some people would clump in 
the blood serum of certain, though not all, other people. 
Evidently not only do red blood cells act as antigens, but 
those of some people are the specific antigens for the normally 
occurring antibodies in the blood of others. There are, in fact, 
two such antigens in human red blood cells, named A and B, 
and, correspondingly, there are two antibodies in the se- 
rums. Landsteiner and others found that some people had 
both the antigens, some had either one alone, some had 
neither. These are the blood groups AB, A, B, and O, respec- 

Of course, if a person carries a particular antigen, he must 
be lacking in the corresponding antibody; else his blood 
would agglutinate in the vessels and stop the circulation. It 
is not so clear why every person who lacks a particular anti- 
gen should be provided with the complementary antibody, 
but this too is the rule. When suspensions of red blood cells 
are mixed under the microscope with each of several serums 
known to contain particular antibodies, any person's blood 
can be quickly typed, for clumping indicates the presence in 
the cells of the specific antigens for whatever antibodies are 
known to be present. 

The first and most widely known use of this knowledge 
was to make blood transfusions safe, but the distribution of 
the blood groups among relatives early attracted investiga- 
tion, too. Certain parents never had particular blood groups 
represented among their children. These findings are sum- 
marized in Table I. 

Very little analysis is needed to see that the O group be- 
haves as a typical recessive. O by O matings always produce 
only O children, though these may come also from other 

21 Dr. Landsteiner has long been in America, associated with the Rocke- 
feller Institute. He was awarded the Nobel prize for medicine in 1930. 



Blood groups 
of parents 


Table I 

Blood groups 

which may occur 

in children 




O, B 

O, B 

O, A, B, AB 

A, B 

A, B, AB 

A, B, AB 

A, B, AB 

Blood groups 

which do not occur 

in children 

A, B, AB 






(From L. H. Snyder, The Principles of Heredity, p. 96, D. C. Heath, Boston, 

crosses; while O-type children never occur when one of the 
parents is of group AB. On the other hand, A by B type par- 
ents may have children of group AB, so that here we find 
blending. All the results can be explained if we assume the 
blood groups are due to three alleles, A A and A B blending, a 
recessive to both. The first two produce the antigens in- 
cluded in their symbols as superscripts, while a is ineffective 
in producing either. In the accompanying diagram (Fig. 20) 
the possible genotypes within each of the four blood groups 
are given, and the gametes each genotype will produce. By 
the proper combinations of these gametes for any given mat- 
ing, the empirical results of Table I can be obtained. 

From the table we can also see that neither antigen A nor 
antigen B ever appears in a child's blood unless it was present 
in at least one of the parents. This, which is merely a particu- 
lar instance of the general behavior of dominants, has been 
used widely in legal medicine to determine parentage. 

A few years ago there was a famous "baby case," in which 
one of two mothers who went home from the hospital at the 



same time claimed she had received the wrong baby, a claim 
the other mother disputed. Sometimes an analysis of the 
blood groups can instantly clear up any such doubt. In this 
instance, for example, two of the parents were each of group 
O, while the baby they had been given was of group A, mani- 
festly not their own. In the other family, the father belonged 

The Majo r Blood Grou ps 




Fig. 20. The major blood groups. A diagram to illustrate the genotypes of 
the individuals belonging to each of the four major blood groups, and the 
kinds of gametes they produce respectively. The chromosomes carrying the 
three alleles, A&, AB and a are differently shaded. 

to group O, the mother to group AB, and their presumed 
baby was of group O— again an impossibility. But the herit- 
age of the babies would fit very well into the opposite fami- 
lies. It was evident that an error had been made, and the 
court ordered the babies exchanged. Very frequently, of 
course, blood tests cannot show anything decisive in these 
cases, as often either of the disputed sets of parents could 
have produced either child. Unfortunately this is especially 
likely to occur in cases where paternity alone is questioned, 
since blood tests can reveal only whether a particular man 
could or could not have been the father, and the former indi- 
cation is several times as likely as the latter. 

The blood groups have also been used in studies of racial 


relationships, since the proportions of the four groups in the 
population vary from race to race. It is interesting, too, that 
these same blood groups occur among the great apes. 

Whenever, in such studies, the analysis of the four stand- 
ard groups remains inconclusive, recourse may be had to 
another pair of antigens found to be present in human red 
blood cells, but unaccompanied by normal antibodies. These 
antigens are called M and N, and depend, respectively, on a 
single pair of alleles, M and N. As neither of these is dom- 
inant over the other, the genotype M/N results in the produc- 
tion of both antigens. In the accompanying diagram are 
given the phenotypes (blood groups); their respective geno- 
types; and the types of gametes formed by each (Fig. 21). 

The M-N 'S ystem 

Phenotype M MN N 

r T 7""^~H 

J f**\ 1 (MS 1 (JL\ ' 

Genotype 1 f 25 ) | ( S5 J 1 ( HH ) j 

Gametes 1 («■») i(«"*) l«aa)i (ess) 1 

1 \^y iWWi v — s 1 
1 ± j- 1 

Fig. 21. The minor blood groups, illustrating the genotypes of individuals of 
each group and the kinds of gametes they produce. 

Alleles do not necessarily affect the same trait. In Drosoph- 
ila, for example, there is a gene which in one form pro- 
duces a disarrangement of the orderly rows of facets in the 
compound eye of the fly. An allele which produces no dis- 
cernible effect on the eye causes neat little scalloped inci- 
sions at the tips of the wings. The heterozygote is completely 
normal, without either facet disarrangement or notches on 
the wings. In another allelic series one member, known as 
vortex, causes peculiar volcano-like vortices on the thorax; a 
second, called oblique, lops off the wing-tips; while a third, 
dumpy, does both. The heterozygote between dumpy and 


vortex has vortices on the thorax but normal wings. Simi- 
larly, the dumpy/oblique heterozygote has lopped wings, but 
a normal thorax. The vortex/oblique heterozygote is per- 
fectly normal, having neither characteristic! 

These facts are enough to show us that alleles may interact 
in a number of possible ways. As a result, dominance and 
the phenotypic ratio vary from case to case. Were it not for 
the constancy of the genotypic ratio, based upon the nature 
of meiosis and syngamy, no order could be discerned in 
hereditary phenomena! 

The inheritance of two or more independent pairs 
of alleles 

Having now seen how a single pair of genes behaves in 
inheritance, we are prepared to follow two independent pairs 
at once. Since inbreeding of the offspring, necessary for an 
analysis of the second generation (F 2 ), is taboo in human 
society but is permissible in animal-breeding, this time we 
shall use guinea pigs. If we mate a guinea pig from a breed 
pure for rough coat and colored fur with one from a breed 
pure for smooth coat and white (albino) fur, the offspring 
(F x ) are all rough and colored. Rough (R) and colored (C) 
are therefore dominant to smooth (r) and white (c a ). The 
gametes of the first parent all carried R and C, and those of 
the second r and c a . Moreover, if independent, these pairs 
must lie in separate pairs of chromosomes, as in Fig. 22. 

Non-homologous chromosomes, as we have learned, assort 
at random during meiosis. In the doubly heterozygous F x off- 
spring, this results in four kinds of gametes, one for each of 
the four possible combinations of the genes. Two of these 
are the original combination, R;C and r;c a , while the other 
two, R;c a and r;Cr are new. These occur in both eggs and 
sperm, so that at syngamy 4 X 4 ° r l6 combinations result 
(Fig. 23). Adding these classes, we get 9 rough, colored |; 

22 Symbols for genes located in different chromosomes are separated by a 




Kinds of 

Genotype of 
Offspring (F J 

Fig. 22. Results of crossing two purebred strains of guinea pigs differing in 
two pairs of independently assorting characteristics. R, rough coat, dominant; 
r, smooth coat, recessive. C, colored coat, dominant; c a , albino, recessive. 

3 rough, white □; 3 smooth, colored • : and 1 smooth, white 
O • This phenotypic ratio was first discovered by Mendel in 
peas. For example, peas with round yellow seeds crossed with 
those having wrinkled green seeds produced only round yellow 


R;C R;c l 



R;C # 


S perms 

r;C ±;± 

r;c l 

R.C m 
R'C U 

R.c a m 
R'C " 

R'C " 

R'C " 


R.C m 
R'c aU 

R'c a0 

R'c aU 

£..c a n 

r;c« u 

R.C * 

R.c a * 



r!.C * 

r.c a m 
r'C W 

R.C * 
r'c aU 

r c a 

f S 

r.C m 

r'c aW 

r -Ko 

r c a 

Genotypes and 

Phenotypes of 


Fig. 23. Recombination in the second generation, after a cross between two 
purebred strains differing in two pairs of independently assorting character- 
istics. See Fig. 22. Phenotypes, g| rough, colored; □ rough, white; £ 
smooth, colored; Q smooth, white. Arrows indicate similar genotypes. 



seeds in ¥ lt and in F 2 produced 3 1 5 round yellow, 1 o 1 wrinkled 
yellow, 108 round green, and 32 wrinkled green seeds. This is 
a very close approximation to the expected 9 : 3 : 3 : 1 ratio. 

The genotypes are nine in number, in the following ratio 
(corresponding genotypes are connected by arrows in Fig. 
23): 1 R/R;C/C : 2 R/r;C/C : 2 R/R;C/c« : 1 R/R;c a /c« : 
4 R/r;C/c a : 1 r/r;C/C : 2 R/r;c a /c a : 2 r/r;C/c a : 1 r/r;c*/c*. 
Hence there are four genotypes among the doubly dominant 
individuals, two among each of the singly dominant groups, 
and only in the case of the doubly recessive group can one be 
sure of homogeneity. Inasmuch as each genotype behaves 
differently in breeding, any attempt to breed merely accord- 
ing to the phenotypical classification is almost certain to go 

How can the breeder, then, find out the genotype? The 
backcross to the doubly recessive type will reveal it, for then, 
just as in the crosses with a single pair of factors, the off- 
spring will have phenotypes which correspond to the gametes 
of the animal or plant tested. If, for instance, we cross a 
rough, colored hybrid guinea pig (R/r;C/c a ), which produces 
the four types of gametes found in Fig. 23, with a smooth, 
white mate-which, being homozygous, forms only one sort 
of gamete-we obtain the result shown in Fig. 24. Four kinds 
of offspring, corresponding to the four kinds of gametes 
formed by the hybrid, occur with equal frequency. A cross to 
a type recessive for all the pairs of genes being followed is 
therefore a test-cross, which enables us to determine the 
genotype of any individual. 

To go further and show how three independent pairs of 
factors behave in inheritance would only be laborious and 
would involve no new principle. The Mendelian principle 
of the independent assortment of gene pairs, just illustrated, 
may be formulated in a simple mathematical way and ex- 
tended to any number of independent pairs of genes. 

The formula 2 n gives the number of gametic combinations 
for any number of independent pairs of genes on the basis 



r'c a 


R;C R;c a r;C 

r.c_ a Parental 
r'c a Genotypes 

a , Kinds of 

r;c ( 

r;c ( 


R.c a 
r'c a 


r'c a 



of Offspring 

Fig. 24. Results of crossing a hybrid for two pairs of characteristics with a 
mate homozygous for both recessive traits; the test-cross. Phenotypic ratio is 
1 rough, colored : 1 rough, white : 1 smooth, colored : 1 smooth, white. 

of chance, just as for chromosomes (see p. 68). Gametes also 
unite by chance, and each individual is therefore the com- 
bination of two gametes whose individual genotypes each 
have a probability of i/ 2 n. What is the chance for the union 
of any two particular combinations? This is given by a 
well-known law of probability which states that the chance 
of coincidence of two or more independent events is the prod- 
uct of the probabilities of each of the events. For example, the 
chance that any penny will fall heads is i/ 2 . The chance that 
two pennies flipped together will both fall heads is there- 
fore 1/2 X !/2 = l A> tne product of the probabilities that 
either alone will fall heads. Applying this principle to any 
number of pairs of genes: 

2 pairs 

2 n x 2 n 
2 2 X 2 2 = 16 

3 pairs 

2 n x 2 n 

2 3 X 2 3 = 64 

These expressions may be factored: 

(2 X 2) (2 X 2) = 16 and (2 X 2) (2 X 2) (2X2) = 64. 

When one allele is dominant and the other is recessive, the 
phenotypic ratio for the F 2 , we found, is 3 dominant to 1 


recessive (3:1). We may substitute this ratio for its equiva- 
lent expression (2 X 2) in the equations, since both repre- 
sent the product of the gametic combinations: 

(3 : 1) (3 : 1) = 16 and (3 : 1) (3 : 1) (3:1) = 64. 

Multiplying out, we then get the phenotypic ratios: 

9:3:3:1 = 16 and 27 : 9 : 9 : 9 : 3 : 3 : 3 : 1 = 6 4- 

The largest class is that displaying all dominant traits, next 
largest are those displaying one less dominant, and so to 
the smallest class, which will have no dominant genes. 23 The 
application of the formula will readily yield the phenotypic 
ratio for any number of independent pairs of alleles, each 
yielding a 3 : 1 ratio alone. 

If two particular alleles blend instead of exhibiting clear 
dominance and recessiveness, the phenotypic ratio for such 
a case (1 : 2 : 1) is simply substituted for 3 : 1. The conse- 
quences can thus be calculated for any number of pairs of 
genes in any combination of allelic relations, simply by 
algebraic multiplication. 

Here, as in the arrangement of the chromosomes on the 
meiotic spindle, chance prevails. Here, once again, there is an 
exact parallel between the behavior of genes and chromo- 
somes. The pairs of chromosomes assort at random— so do the 
independent pairs of genes we have been considering. 

This has been a long section. It will be well to pause and 
review what we have learned of heredity thus far: 

1. Heredity is due to units (genes) which, because of 
syngamy, are paired (alleles) in individuals. 

2. The process of meiosis results in the segregation of 

23 It is worth noting that the first number of such a phenotypic ratio gives 
the number of different genotypes present. Thus there are, respectively, 9 
and 27 genotypes in the two crosses illustrated here. 


3. Syngamy of a particular sperm and egg is a product of 
chance and, hence, brings about a random recombina- 
tion of alleles from the two parents. 

4. While present in the same cell, alleles interact to affect 
traits in a variety of ways (complete dominance of one, 
incomplete dominance, equal blending; alleles do not 
even always affect the same trait). 

5. The genes themselves are unaltered by their interaction. 

6. Gene pairs which are inherited independently show ran- 
dom assortment at meiosis. 

Though not expressed in his terms, these are the principles 
Mendel discovered. Only the further observation of the 
parallel behavior of genes and chromosomes came later, open- 
ing new avenues of interpretation, which we are now ready 
to explore. 


Mendel's discoveries of the unitary nature of the heredi- 
tary material and of the role of chance in providing recom- 
binations of the units in gametes and zygotes were made dur- 
ing the very period when Oskar Hertwig and Strasburger were 
led to assert that the chromosomes must be the carriers of 
heredity. Yet neither the demonstrations of the persistent in- 
dividuality of the chromosomes nor the unique manner in 
which they are duplicated and distributed in equivalent sets 
to each new cell, through the mechanism of mitosis, furnished 
final proofs of the "Chromosome Theory of Heredity." The 
rediscovery of Mendel's work brought out at once the striking 
series of parallels between the deduced behavior of the hered- 
itary factors and the transmission of the chromosomes in 
meiosis and syngamy. It was seen that in gametes the chromo- 
somes are unpaired (haploid)— while, to account for the facts, 
so must be the alleles. In the zygote, and in all its descendant 
somatic and prospective germinal cells, the chromosomes are 


paired again (diploid), with a maternal chromosome corre- 
sponding to each paternal chromosome— and so are the alleles. 
At meiosis homologous chromosomes disjoin— and so do 
alleles. Different pairs of chromosomes assort at random— and 
so do the pairs of genes we have considered. 

All these facts serve to strengthen our belief in the theory, 
yet none of them are conclusive. It is really to the exceptions 
to typical "Mendelian" inheritance that we must turn for the 
most convincing evidence that in the chromosomes, whose 
nature we can study and whose behavior we can to some ex- 
tent learn to control, lie the genes, marking the ultimate goal 
in our quest for an understanding of life. 

As the first exception, we learn that Mendel's principle of 
the independent assortment of gene pairs is not always appli- 
cable. The number of genes is much larger than that of their 
chromosome-carriers; hence a number of genes must lie in 
each of the chromosomes. Consequently, genes in the same 
chromosome cannot be transmitted independently in cell 
division; they are linked. Moreover, since at meiosis each 
chromosome has a partner from which it disjoins, the genes 
in any one chromosome and their alleles in its homologue 
are not transmitted independently either. Together they 
form one "linkage group." Only gene pairs in different pairs 
of chromosomes can assort independently. 24 Consequently the 
number of linkage groups corresponds to the number of 
chromosome pairs. 25 

24 Mendel found independent assortment of all seven of the pairs of alleles 
he studied in the pea. This was an amazing chance, for there are only 
seven pairs of chromosomes in the pea! But for a qualification of this 
generalization, see pp. 116-117. 

25 This relation was first predicted by W. S. Sutton, while a graduate 
student at Columbia University, in 1903. In his thesis for the Ph. D. degree, 
he proposed the theory that the paired Mendelian factors lie in paired 
chromosomes, such as he had been studying with Montgomery in lubber 
grasshoppers. He also pointed out that the independent assortment of 
different pairs of genes is due to the chance position of the maternal and 
paternal chromosomes of different pairs upon the spindle at the reduction 
division. The meteoric rise of genetics as a science has been little more 
than the proving of these three postulates. Sutton, however, choosing medi- 


The first case of linkage turned up in the sweet pea 
(Lathyrus), in 1906. A cross involving two pairs of genes 
showed that the gene for purple flowers and the gene for 
cylindrical pollen grains were inherited together, and, con- 
versely, those for red flowers and disk-shaped pollen. Every 
form of plant and animal subjected to breeding since that 
time has, when sufficiently analyzed, yielded additional in- 

An exact correspondence between the number of linkage 
groups and the number of chromosome pairs has not always 
been found, mainly because of the great labor involved in de- 
termining it, especially when the haploid chromosome num- 
ber is high. But in those organisms which have been studied 
intensively and which have a low chromosome number, such 
as Indian corn, sweet pea, and some six species of Drosophila, 
there is perfect correspondence. In Drosophila melanogaster 
several thousand genes have been tested, and each falls into 
some one of four linkage groups corresponding to the four 
pairs of chromosomes (i. e., the haploid number). 26 The suc- 

cine as a profession, had no further part in the advance of the science he 
played so large a part in founding. 

26 There is one mechanism, however, which may reduce the number of 
linkage groups below the haploid chromosome number. In Chap. I (p. 17), 
we learned that x-rays often break chromosomes, and that fragments may 
become reattached elsewhere. Thus pieces may be interchanged between 
chromosomes of different pairs, a situation known as a "translocation." Since 
pairing is ultimately a property of genes, each compound chromosome re- 
sulting from translocation will have, at meiosis, more than one partner with 
which to pair and from which to separate. The contrast between normal 
pairing and that when a translocation is present will be clear from the 
diagram below (Fig. 25). The two original pairs of chromosomes are differently 

Now this situation will affect the linkage of the 

c c a 1 * 1 1 Normal 

genes. Suppose one pair of genes, A /a, to be lo- Pairing 

cated on one of the original pairs of chromosomes aQQA 
(unshaded), and another pair of genes, B/b, to be 
on the other (shaded). Different pairs of chromo- 
somes assort independently. We can then expect 
random assortment for A /a and B/b. But when a 
translocation has involved two of the chromosomes of these pairs, two of these 
hitherto independently assorting genes— a and B, for example— will now lie in 


cessful confirmation of our prediction that the genes will be 
inherited in linkage groups if they are located in the chromo- 
somes serves as further evidence to convince us that our the- 
ory is correct. 

Now what alteration does the existence of linkage make in 
the pattern of heredity? We have seen that the number of 
possible combinations which can be made up by taking at 
random one member from each pair of units is 2™, where n is 
the number of such pairs. In meiosis n is the haploid chromo- 
some number. Then 2 n is well up in the millions for man- 
kind, but in any organism which has a low haploid number 
or in which translocations reduce the number of linkage 
groups to the equivalent of a low haploid number, it is rather 
small. In Drosophila, for instance, 2 n is only 16. Wherever 
the genes within each chromosome are inseparable, the maxi- 
mum number of variant offspring from a cross between two 
individuals which have no two homologous chromosomes 
exactly alike in any of the linkage groups is then (2 n ) 2 . It 
would amount, for Drosophila, to only 256. On the other 
hand, if the individual gene pairs were able to assort at ran- 
dom, 2 n would amount approximately to 2 3000 , and this num- 

the same compound chromosome. They will therefore be inherited together! 
That will be true for all the genes in this compound chromosome, although 
they were originally of different linkage groups; and, of course, those in the 
other compound chromosome will be inherited together, too. Moreover, since 
none of these four chromosomes can now assort independently of the others, 
all the genes of the two original linkage groups will form one interdependent 
group. A translocation changes two linkage groups into one. 

Translocations, like gene mutations, occur spontaneously as well as through 
the action of x-rays. Since they may involve interchanges between more than 
two pairs of chromosomes, we may have larger groups of partially pairing 
chromosomes, six, eight, or more. Correspondingly, three, four, or more 
linkage groups may become combined into one. This is especially common 
in certain species, like the evening primrose (Oenothera) and the Jimson 
weed (Datura); it is the most probable reason why in some forms, such as 
the grouse locust (Apotettix) and the West Indian guppy (Lebistes), which 
have numerous chromosomes, all the genes nevertheless appear to be in- 
herited in a single linkage group. This situation is after all not very com- 
mon, and we are not likely to meet with it in any of the organisms in which 
we are most interested. Its main import is evolutionary. 


ber squared would be utterly inconceivable. Thus a limit is 
set to variation by the linkage of the genes. The fewer the 
linkage groups, the more rigid will be the restriction on the 
number of combinations. 

Actually, there is much more variation than this would 
lead us to expect. The fruit fly, for instance, is certainly not 
limited to 256 gene combinations per couple. How is this? 
If linkage were complete, two pairs of genes A/a and B/b 
belonging to the same linkage group (with A and B together 
in one chromosome and a and b together in its homologue) 
would always segregate in the combinations AB and ab. Yet 
even in the first observed case of linkage, that in the sweet 
pea mentioned at the beginning of this section, it was ob- 
served that these original combinations were often broken 
up, and recombinations (Ab and aB) appeared. Evidently 
genes in the same chromosome may part company and come 
to lie in homologues. In fact, this capacity is quite general, 
for every organism in which linkage has been studied has 
revealed this sort of recombination. Yet linkage is not nulli- 
fied by it, as we shall see. 

Suppose we take an example from maize. A certain reces- 
sive gene (su) produces sugary endosperm in the kernels, 
making sweet corn fit for our tables rather than the starchy 
field corn we feed to livestock. It is linked to another reces- 
sive gene called lazy (la), which produces such a weakening 
of the stalks that the plants straggle and lie prone on the 
earth. By crossing a plant heterozygous for these two genes 

/su la\ . , / su la\ 

( c — — ) with a homozygous recessive I — ) , we can test 

the former for the kind of gametes it produces (as shown in 
Fig. 26). 

All four possible types are present in the offspring of our 
cross, both the two original combinations and two recom- 
binations. In looking over the offspring we would, no doubt, 
notice that the recombinations were much scarcer than the 
original combinations. In a large number, which should 



be counted to get an accurate measure of the ratio, there 
would turn out to be approximately 45.5 per cent of the 
sugary lazy plants, a like amount of the Starchy non-lazy, 
4.5 per cent of the Starchy lazy, and a like amount of sugary 
non-lazy. The total recombination for these gene pairs is 
therefore 9.0 per cent. 


(su la) (SzN^a) Qsu la) 

(S La) ^>^ Qu la) 

Kinds of Gametes 
Csa id) Q la) (ja La) Q_ la) (su la) 


su la 



S La su La 

S la 

su la 

su la 
su la 

v5 La 
su la 

su La 
su la 



Result : Original combinations: sugary lazy; Starchy non-lazy. 
Recombinations: sugary non-lazy; Starchy lazy. 

Fig. 26. Recombination between the linked characters sugary endosperm 
(su) and lazy stalks (la) in maize, as shown in a test-cross. In the progeny all 
possible combinations of the characters and their opposites occur in equal 
proportions, regardless of whether the combinations are the original ones 
(sugary lazy; Starchy non-lazy) or are recombinations (sugary non-lazy; 
Starchy lazy). But the original combinations and the recombinations are not 
equally frequent. 

Now we know that all the observed recombinations must 
have taken place in the heterozygous parent. 27 The pheno- 
types of the offspring, therefore, reflect the genotypes of the 
gametes, both the original kinds and the recombinations, 

27 It is obvious, from Fig. 26, that there can be no recombination in a 
homozygous individual. Fven when one of two pairs of genes is heterozygous, 
all gametes formed must still be identical; AB/aB can produce only AB and aB 


which are produced by this parent. We can go a step further. 
Since one parent furnishes only a single sort of gamete (100 
per cent su la), the various frequencies of the phenotypical 
classes must correspond to the different frequencies of the 
types of gametes supplied by the other— the heterozygous- 
parent. There must then have been 45.5 per cent su la gam 
etes; 45.5 per cent S La; 4.5 per cent su La; and 4.5 per cent 
5 la. This is a particular instance of the more general fact 
that the frequency of any class is the numerical product of 
the frequencies of the gametes uniting to form it. 

To sum up, the test-cross has made apparent, in the pheno- 
types of the offspring, the gene combinations and their 
frequencies among the gametes of the tested parent. Of all 
crosses, this to the homozygous recessive is the most reveal- 
ing and most valuable to the geneticist and breeder. 

Now, how can recombination take place if the genes con- 
cerned actually lie in the same chromosome? How do alleles 
change places? Observations in both Indian corn and fruit 
fly have demonstrated the general nature of the mechanism. 
In Drosophila, Curt Stern 28 was able to obtain homologous 
chromosomes which were visibly different. By the transloca- 
tion process described a little while ago, one chromosome 
had been broken in two, 29 while the other had a long piece 
attached to it. Known to lie in one of the short pieces were 
two mutant genes, a recessive producing carnation-colored 
eyes (symbol car), and a dominant narrowing the eyes (Bar— 

28 Curt Stern, now at the University of Rochester, is a refugee from Nazi 
Germany. His monographs in German on Advances in the Chromosome The- 
ory of Heredity, Linkage and Crossing Over, and Multiple Allelism are indis- 
pensable to the geneticist: 

"Fortschritte der Chromosomentheorie der Vererbung." Ergebnisse der Biol- 
ogie, Vol. 4, pp. 206-359, 1928. 

Faktorenkoppelung und Faktorenaustausch. "Handbuch der Vererbungswis- 
senschaft," No. 19. Gebriider Borntraeger, Berlin, 1933. 

Multiple Allelie. "Handbuch der Vererbungswissenschaft," No. 14. Gebriider 
Borntraeger, Berlin, 1930. 

29 Both pieces of this broken chromosome segregate normally, as one has 
its original spindle attachment and the other is preserved from being lost 
by translocation to another chromosome (not shown in Fig. 26). 


symbol B). In the homologous chromosome with the extra 
limb were the normal alleles of these two genes. (A + super- 
script is the symbol for any normal allele.) The pair of 
chromosomes may, therefore, be diagramed in the following 

way (Fig. 27). 



Fig. 27. The two modified sex chromosomes of Drosophila melanogaster used 
in the cytological demonstration of crossing over. The broken chromosome 
carried the mutant genes for carnation eye color and for Bar eye; the chromo- 
some with an appendage bore the dominant allele for red eye color and the 
recessive allele for non-Bar eye. (Stern) 

Females of this type and heterozygous for both gene pairs 
were tested by being crossed to carnation non-Bar males. 
As expected, the alleles reappeared mainly in the original 
combinations; but recombinations (carnation non-Bar, and 
Bar non-carnation) were also present among the progeny. 
When their chromosomes were examined, every one of the 
female offspring carrying the original combinations had one 
of the original kinds of chromosomes present in the mother, 
along with an unbroken normal homologue from the father. 
The carnation Bar-eyed ones had the broken chromosome; 
the non-carnation non-Bar had the chromosome with the 
extra limb. But, on the other hand, those showing recombi- 
nations of the genes had new kinds of chromosomes. The car- 
nation non-Bar daughters had two unbroken chromosomes, 
and the Bar non-carnation daughters had a broken chromo- 
some with an extra limb (Fig. 28). In every single case, re- 
combination of the gene had been accompanied by a chromo- 
somal change! 

These types of chromosomes were just what Stern had pre- 
dicted would arise if the chromosomes actually interchanged 
at some point between the two pairs of genes, as shown in 
Fig. 29. 


Original Combinations 
car 3 car+ B+ 

carB + B car-f- 





B + 



Fig. 28. The test-cross offspring of females of the genotype in Fig. 27, show- 
ing how recombination of the genetic characters was accompanied by change 
in the chromosomes. (Stern) 

When might this process, known as crossing over, occur? 
It had long been known that the prophase of the first meiotic 
division is greatly extended. During this time the homolo- 
gous chromosomes are at first intimately paired. Later, while 
still twisted about one another, they loosen up, so as to form 
a number of internodes and nodes. (The nodes where the 
chromosomes cross are known as chiasmata.). Each node is 
believed to indicate that the homologous chromosomes have 
broken and have exchanged equivalent segments during the 
period when they were intimately paired (Fig. 29). 



Fig. 29. The mechanism of crossing over: fracture of homologous chromo- 
somes at identical levels and exchange of equivalent segments. 

Genes which lie in the same chromosome, then, do recom- 
bine, and this recombination is brought about by an ex- 
change of segments between homologous chromosomes. We 
need go no further to establish our generalization that the 
limitation of gene combinations which linkage brings about 
can be counteracted by the possibilities of recombination 
through crossing over. But to what extent does this recom- 



bination actually occur? Can it really nullify the effect of 
linkage? In exploring these questions, we shall incidentally 
get a glimpse into the methods which enable the geneticist to 
say with confidence: "Here is a map of the invisible genes. 
This is their order and arrangement within each chromo- 
some. Each known gene is here traced to its submicroscopic 
locus." The human mind has penetrated the secrets of life 
in no more revealing way. 

When a chiasma is formed, the homologous chromosomes 
have exchanged segments, as we have seen (Fig. 29). If, then, 
the chromosomes carry a great many genes, such segments 
must assuredly carry more than one gene apiece. Crossing 
over consequently should result in the recombination, not of 
single genes, but of whole blocks of genes. In our example 
we have failed to detect this because only two gene pairs 
were heterozygous. Had we had several such heterozygous 
pairs, we could have found out more about the nature of 
crossing over. 

This suggests that we next determine the frequency of 
crossing over between a number of genes in the same chromo- 
some. Our results will now include various frequencies, al- 
though for any two particular genes, under the same condi- 
tions, the value appears to be constant. A and B, for example, 
cross over 4 per cent of the time, while A and C cross over 10 
per cent of the time. What does this signify? 

A. H. Sturtevant, 30 in 1913, realized that if the genes are in 
a linear series, then the farther apart any two genes lie, the 
higher the chance of a crossover between them. This would 
account for the different frequencies of crossing over between 
different genes. How can the hypothesis be tested? If the 
assumptions we have made are sound, it should be possible, 


30 The early development of Drosophila genetics was due largely to Thomas 
Hunt Morgan and three of his students: Alfred H. Sturtevant, Calvin B. 
Bridges, and Hermann J. Muller. Sturtevant and Muller laid the founda- 
tion for our understanding of crossing over, while Bridges, among other 
things, pioneered in mapping the chromosomes. 


by determining crossing-over frequencies, to fix the order of 
the genes, and to estimate relative distances between them; 
otherwise not. For example, A, we have supposed, crosses over 
with B 4 per cent of the time, with C 10 per cent of the time. 
Let B lie four units from A, and C ten units from A. How 
far is B from C? A little analysis shows us that, if the linked 
genes are in a line, it will depend on whether B and C are on 
the same side of A, or on opposite sides: 

B C B 4 A 


— 10 > 

BC should be either AC - AB or AC + AB. In the first case, 
B and C would cross over 6 per cent of the time; in the 
second, 14 per cent. It is a simple matter to determine, by 
test-cross, which is true. Usually the whole matter can be 
settled at once by testing an individual heterozygous for each 
of the three genes. (This is known as a three-point cross.) 

Here is an example from Drosophila, in which more 
chromosome mapping has been done than in all other organ- 
isms together. Individuals carrying a mutant which reduces 
the wings to mere stubs (vestigial) were crossed with black- 
bodied, purple-eyed mates (two mutants). 31 (It had already 
been determined that these genes all belong to the same 
linkage group.) Female offspring, 32 all normal-looking, since 
each of these genes is recessive, were then test-crossed, that is, 
were mated with black-bodied, purple-eyed, vestigial-winged 
homozygous males. Their offspring, the F 2 generation, were 
mostly either vestigial-winged (868) or black-bodied, purple- 
eyed (843) flies. These were non-crossovers. But every other 

si To save endless repetition of normal phenotypes, we commonly describe 
each type only by its mutant characters. Thus, the vestigial-winged female 
fly, it is to be understood, has red eyes and gray body color, while her 
black-bodied, purple-eyed mates have wings of normal length. 

32 Females must be used for testing crossing over in Drosophila because 
there is ordinarily no crossing over in males. 


possible combination of these three traits was also repre- 
sented. In a total of 2,012 flies: 

i these were recombinations of 

black and vestigial; and of 
black and purple. 

i these were recombinations of 

black and vestigial; and of 
purple and vestigial. 

i these were recombinations of 

black and purple; and of 
purple and vestigial. 

If we put any three genes in a row, there can be only two 
intervening regions (1 and 2) in which crossing over might 
occur (Fig. 30). Where, then, does the third pair of comple- 
mentary classes come from? Have the chromosomes perhaps 

Jsl ar b=black 

-m Z ► pr= purple 

vg= vestigial 

b + jor^ vg 

Fig. 30. The regions (i, 2) in which crossing over may be detected when a 
pair of chromosomes carries three mutant genes at different loci, b, black 
body color; pr, purple eye color; vg, vestigial wings; b+, &+, vg\ respective 
normal alleles in Drosophila melanogaster. 

crossed over in both regions simultaneously? If the chance of 
any such "double crossing over" is random, it would be the 
product of the frequencies of crossing over in each of the re- 
gions; and one complementary pair of recombinations ought 
then to be much scarcer than the others. When we calculate 
the percentages of recombination 33 between each two genes, 
we get 5.8 per cent for black and purple, 9.8 per cent for pur- 
ple and vestigial, and 144 per cent for black and vestigial. 
This indicates that black and vestigial are farthest apart, and 

33 The percentage of recombination for any two genes is simply: 
number of individuals showing recombination 
total number of individuals 


1 lr, 

that purple is in the middle. Then, checking to see whether 
the complementary classes lowest in frequency equal the prod- 
uct of the major classes, we find: 5.8 per cent of 9.8 per cent 
= 0.6 per cent; and 1 1/2012 = 0.6 per cent. Our hypothesis 
seems to be right. 

We can, then, represent the relations of the three genes, 
the varieties of crossing over, and the gametes formed, as in 
Fig- 31- 

Crossing over Crossing over Crossing over 

in region 1 in region 2 in both regions 

Fig. 31. Diagram illustrating crossing over by regions, in a fruit fly of the 
genotype shown in Fig. 30. For simplicity, labeling of the normal alleles of 
the three mutant genes is omitted. 

In calculating how often black and vestigial cross over, we 
must count each double crossover between them twice. Yet 
these double crossovers did not result in any recombination 
of black and vestigial. 34 Hence, we must add twice the fre- 
quency of the double crossovers to the 14.4 per cent of re- 
combinations of black and vestigial, 2 X 0.6 = 1.2; and 14.4 
+ 1.2 = 15.6. This value amounts exactly to the sum of the 
crossing over in the regions between black and purple and 
between purple and vestigial (5.8 + 9.8 == 15.6 per cent). 

34.Every crossover between black and purple recombines these genes- and 
so, too, for purple and vestigial. But every crossover between black and 
vestigial does not recombine these two genes, since, in any region as Ion- as 
this, double crossing over may occur. In shorter regions one crossover pre- 
vents any other close to it. This is the phenomenon of interference. Because 
of these double crossovers, the recombination of black and vestigial (144 
per cent) must always be less than the sum of the recombinations of black 
and purple (5.8 per cent) and of purple and vestigial (9.8 per cent) This 
explains why recombination, for relatively distant genes, is always less than 
the amount of crossing over between them. 


This is possible only if the genes are arranged in a linear 


It would be rash to say that the percentages of crossing 
over give us any exact measure of the relative lengths of the 
intervals between genes, as many factors (x-rays, temperature, 
age, sex, proximity to end of chromosome or spindle attach- 
ment, for instance) can radically alter the frequency of cross- 
ing over. But they do serve to indicate approximate dis- 
tances and to define the serial order of the genes. We may, 
then, map them in order on a scale, each unit of which repre- 
sents 1 per cent of crossing over. 

This is a sample of the method by which a geneticist maps 
chromosomes, a preliminary task essential to the analysis of 
still finer details, the quirks and crotchets of the hereditary 
pattern. Often enough, these may lead to important discov- 
eries-but we must leave them out of our discussion, if some- 
what regretfully, and turn our attention to other aspects of 
more immediate significance. 

What, for instance, is the probability that recombination 
will occur? How extensive is the variety, among the individ- 
uals of a progeny or a population, that can be brought about 
by crossing over? At one extreme we can find genes which lie 
in the same chromosome but are so far apart that they will 
cross over 50 per cent of the time, or more. As 50 per cent 
recombination amounts to random assortment, which holds 
for genes in different pairs of chromosomes, this is normally 
the maximum recombination value. 35 Genes as far apart as 
this behave as though located in different chromosomes. In- 
deed, their membership in the same linkage group can be 
detected only when they are tested with some intermediate 
gene, with which each crosses over less than 50% of the time. 30 

35 Two genes may cross over more than 50 per cent of the time, but they 
cannot recombine more often than this, since multiple crossing over then 
tends to replace them together as often as they are separated. 

36 if b crosses over 30 per cent of the time with A, and 45 per cent with C, 
both A and C will show linkage with B. Yet A and C, 75 crossing-over units 
apart will assort at random. This will account for the occasional instances in 
which there appear to be more linkage groups than pairs of chromosomes. 


The length of a chromosome in this way becomes a crucial 
factor in controlling the total amount of recombination 
among linked genes. If, for example, a chromosome is 100 
crossing-over units in length, the average gene in that chromo- 
some will assort at random with 25 per cent of the genes in 
its own linkage group; while, if the chromosome is as much 
as 200 units long, the average amount of random recombina- 
tion between its genes will rise to more than 50 per cent! This 
is no mere theoretical digression— chromosomes frequently at- 
tain such lengths! Two of the four kinds of chromosomes in 
Drosophila melanogaster attain 100 crossing-over units in 
length; in a relative, Drosophila virilis, with six kinds of 
chromosomes, there are two of more than 200 units each, two 
are about 175 units in length, one is about 125 units, and 
only one is short. In Indian corn three of the ten chromo- 
somes are more than 100 units, and three more reach 75 
units, or more, in length. The number of possible chromo- 
somal combinations in the gametes (2 n ) is only 16, 64, and 
1,024, m these three organisms, respectively. But so great 
are the lengths of the chromosomes that the number of ele- 
ments assorting at random is rendered greater than the hap- 
loid chromosome number. This amounts to increasing the 
exponent in our formula, and is enormously effective in rais- 
ing the number of possible combinations. 

From this first extreme of random assortment between dis- 
tant genes belonging to the same linkage group, we pass 
through a middle terrain where recombination is of varying 
amount, from 50 per cent down. Here the contribution to 
the total amount of recombination grows less and less. Never- 
theless, the very possibility of such recombination, though 
ever so slight, is an important thing, for it means that every 
theoretical genie combination is ultimately possible. Besides, 
whenever a particular combination of genes within a single 
linkage group is but rarely formed, it will, once formed, be 
all the more likely to stick together, since both combination 


and recombination depend on the same frequency of crossing 

At the other extreme of linkage, we find those genes which 
cross over only once in a thousand or ten thousand times. 
Even these, when they do cross over, can, like others which 
recombine oftener, ultimately enter into any genie combina- 
tion. Suppose, however, that two genes never cross over, or 
that they do so rarely enough to escape observation— what 
then? We must admit that we have no way, at least for the 
present, to distinguish them as separate genes at all. We can- 
not see separate genes with our present techniques, nor can 
we be sure that even the many individual bands of the flies' 
salivary gland chromosomes correspond to single genes. We 
cannot define a gene by mutation, for that, as we have seen 
(p. 79), is a mixed category and is itself defined by the gene. 
We cannot define a gene by its phenotypic effects, for one 
gene may have many or few or even none that are apparent. 
We cannot define it by Mendelian behavior, for that, as we 
have seen (pp. 103 f.), depends on the nature of meiosis and 
syngamy, and the units of those processes are not genes, but 
chromosomes. What do we mean by a gene? There is as yet 
no practicable working definition but this: A gene is a single 
member of the linear series of hereditary factors within each 
chromosome. Its unitary nature is defined by its separability 
from its neighbors through crossing over. The gene has 
meaning only in the light of linkage and crossing over. These 
two phenomena, acting in opposition, regulate the amount 
of reassortment of the genes. Their relative strength in any 
species helps to determine whether there will be great diver- 
sity or marked uniformity among the individuals within any 

The mechanism of crossing over throws light on yet an- 
other process we have discussed, the process of meiosis. If we 
look back at Fig. 11, we can see that when the chromosomes 
pair at the beginning of meiosis— at the time when crossing 
over must take place— each chromosome is already duplicated. 



Now at any given level of a chromosome pair, crossing over 
takes place only between two strands out of the four, and 
always between two strands of different origin— never be- 
tween the strands that have just arisen by duplication from 
one. Let us see, in Fig. 32, what effect this will have. 

No crossing over 


Crossing over 


All Alleles disjoined Alleles not disjoined 

Fig. 32. Diagram illustrating how the first meiotic division brings about the 
segregation of all alleles when there has been no crossing over, but of only 
some of them {A and a, but not B and b) when crossing over has occurred. 

Mendel established the principle that the effect of meiosis 
is to segregate alleles. From Fig. 32 it is evident that this 
can be accomplished for all pairs of genes at a single cell 
division only when there is no crossing over. With crossing 
over, some (A /A and a/a) will segregate; others (B/b and 
B/b) will not. It takes the second meiotic division to provide 
for the segregation of the latter (see Fig. 33), forcing us 

Fig. 33. Diagram illustrating how the second division of meiosis accomplishes 
the segregation of those alleles (B and b) that have not segregated in the 
first division because of crossing over. 


to qualify the statement made earlier (p. 15) that each 
chromosome segregates from its homologue at the first meiotic 
division. With crossing over to take into account, chromo- 
somes can no longer be considered as unbreakable units, and 
segregation, to be effective for all pairs of alleles, must regu- 
larly require two cell divisions. 

We have seen that meiosis and syngamy, with their sub- 
sidiary phenomena of crossing over and linkage, are the major 
processes in the formation of the hereditary pattern of an in- 
dividual. Through them come about the myriad varieties 
of individuals found in most sexually reproducing plants 
and animals. It is only in their light that we can compre- 
hend the broader significance of sex, so potent a factor in the 
evolution of life-forms and in the individual lives of each of 
us. We have next to explore the ways in which the advan- 
tages of meiosis and syngamy to the race have been combined 
with the reproductive function, and to see how the division 
of labor between male and female has been steadily extended 
from the gametes to include an ever greater share of the life 
cycle. Gradually organisms have acquired a sure genetic 
means of determining sex, replacing the haphazard action of 
external environment or the vagaries of developmental forces 
alone. We cannot adequately comprehend the nature of the 
hereditary pattern until we see how this is accomplished, and 
until we see what effects the new mechanism has in turn on 
the transmission of the genes. 


The Genetic Basis of Sex 

SEX is a vital and productive force in man's life. Many 
' have considered it, from a wide variety of viewpoints, 
without appearing to have grasped its basic significance as a 
biological phenomenon. Indeed, it was not possible to do so 
until the genetic and cytological advances of the present cen- 
tury had paved the way. Yet how futile it must be to carry 
the quest for the meaning of sex into obscure realms of emo- 
tion or social influence without that sure sense of direction 
which can come only with an understanding of its biological 
function and evolution. 


Sex to most of us means "man and woman." Biology can, 
first of all, enlighten us as to this interpretation. Were we to 
make even a hasty survey of living organisms, it would be- 
come apparent, first, that all sexual characteristics are asso- 
ciated with the production of either sperms or eggs. Male- 
ness is essentially the capacity to produce sperms; femaleness, 
to produce eggs. Second, we would see that an isolation of 
these two capacities in distinct individuals is a matter of sec- 
ondary importance in the story of sex. Among many of the 
lower animals, each individual has two sets of reproductive 
organs, one male, the other female, and is therefore able to 
produce both kinds of gametes. Among the higher plants 


this situation is by far the most general. The diploid seed 
plant generally either bears flowers carrying both male and 
female structures, or it has separate male and female flowers. 
Relatively infrequent are those plants, like the willow, whose 
male and female flowers are produced on entirely distinct 
individuals. An isolation of the sexes evidently cannot be 
regarded as the most widespread or essential feature of sex; 
it is important, to be sure, and we shall return to a consider- 
ation of its significance, but it is not "elemental" sex. 

Nor does sex as a process necessarily imply cross-fertiliza- 
tion. Usually, of course, two individuals participate, even 
among hermaphroditic forms, such as the earthworm, where 
each individual possesses both male and female reproductive 
organs. But self-fertilization is quite the rule among many of 
the higher plants, such as the members of the pea and bean 
family, where the very possibility of cross-fertilization may be 
virtually excluded by the structure of the flower. Among 
one-celled organisms we can find an even clearer example of 
obligatory self-fertilization. Actinophrys sol is one of those 
heliozoans which, with their hundreds of delicate projections, 
look like indescribably dainty Christmas tree ornaments 
(Fig. 34); at times it interrupts the series of fissions by which 
it reproduces and engages in a sexual interlude. Two nuclei 
form by mitosis within an undivided cell mass. Each then 
passes through the usual two meiotic divisions, and following 
each, one of the resulting nuclei degenerates. Two haploid 
nuclei are left. These, the equivalents of gametes, 1 move 
toward each other, meet, and fuse. A zygote has thus been 

1 In one-celled organisms, a modified form of syngamy known as conjuga- 
tion is frequent. In this process, two individuals make contact by a bridge of 
protoplasm. Then, following meiosis in each, an exchange of haploid nuclei 
takes place, a "male" nucleus from one individual wandering over the bridge 
to unite with a passive "female" nucleus of the other. One or both of the 
conjugants, depending on the species, resumes the normal vegetative life 
and the customary reproduction by fission. The process, as commonly 
described for Paramecium, is in most of the textbooks. Its biological effect 
is exactly that of syngamy, of which, in fact, it is no more than an interesting 
variant, one in which the gametes are nuclei instead of whole cells, and in 


Pseudopod Engulfing Tood 

Contractile Vacuole 

Fig. 34. The common heliozoan, Actinophrys sol. Its raylike pseudopods are 
temporary projections of the protoplasm used in locomotion as well as in 
engulfing food. The contractile vacuole eliminates excess water and some 
wastes. (From Buchbaum's Animals without Backbones. Courtesy of The 
University of Chicago Press) 

formed by the union of gametes derived from the same 
' grandparental" cell. 

If neither differentiation of the sexes nor participation 
of two individuals is the most universal aspect of sex, what 
element of sex is most fundamental? The answer should 
now be clear to us; it was the major subject of Chap- 
ter II— the cycle of meiosis and syngamy. Sex is fundamen- 
tally the adaptation of the individual to this cycle. It is the 
capacity to form haploid gametes which later fuse. 

If this is so, it becomes clear that sex has often been con- 
fused as to meaning and significance. It is not, for instance, 
equivalent to reproduction. Mitosis results in two cells being 

which three divisions, instead of the usual two, are required to form them. 
Only two of these divisions are meiotic; the third is an ordinary mitosis. 
Perhaps this situation is related to the original differentiation of spores and 
gametes, as in Chlorogonium (see pp. 124-125). 


formed from one— that is the basis of reproduction, as was 
pointed out in Chapter I. Syngamy results in one cell being 
formed from two— that is the basis of sex. The two processes 
are diametrically opposite. Yet, in the origin of individuals 
of most forms, both play a part; and so interrelated are they 
that, to most of us, the function of sex has, no doubt, ap- 
peared to be reproduction. Instead, if its function is none 
other than that of the "meiosis-syngamy" cycle, it must be 
the production of variation among the individuals of a fam- 
ily, of a population, of a race, of a species. 


Aside from cell division, there is, as we have already noticed, 
another essential component of reproduction. Cells, newly 
formed by the process of cell division, must loose their hold 
upon one another, must break their ties with parent organ- 
ism and sister cell, and venture forth to start life on their own. 2 
Organisms, whether haploid or diploid, generally arise from 
a single isolated cell. The haploid organism comes from a 
single haploid cell which we may call a spore (a term, to be 
sure, usually somewhat more restricted in its meaning). The 
diploid organism arises from a zygote formed by the fusion of 
two haploid gametes; in other words, a requirement of syn- 
gamy has been superimposed upon the isolated reproductive 
cells. In all other respects these two sorts of reproductive 
cells, spores and gametes, are extraordinarily similar. 

If we compare spore and gamete formation in Chloro- 
gonium, the simplest of the three members of the Volvox 

2 Sometimes, of course, the final severing of these ties is put off for a long 
time, while the young grow at the expense of their parents, receiving sus- 
tenance, care, and protection. This may even go so far that the offspring 
become permanently parasitic upon the parent organism (for example, the 
diploid phase of the life cycle in the mosses or the haploid phase in the 
seed plants). It is amusing to compare with these the lifelong economic 
dependence of children upon their parents in certain strata of our own 


order that served in Chapter I (p. 45) to illustrate the pro- 
gressive limitation of reproduction to special reproductive 
cells, we can get a good idea of their extreme similarity. 
(Meiosis immediately follows syngamy in these algae, as in 
Spirogyra (p. 126), so that all the cells spoken of here are 
haploid.) In Chlorogonium each individual divides into four 
cells. These then break out of the envelope of the parent, 
and become independent individuals; in other words, they 
are spores. However, sometimes a third cell division doubles 
this number before they are set free, and these half-sized 
individuals, otherwise identical with the spores, behave as 
gametes. Each must fuse with another gamete before resum- 
ing cell division; otherwise it perishes. From the resulting 
zygote there forms a cyst which enables the organism to sur- 
vive adverse conditions, and from it, by meiosis, there will 
arise four vegetative individuals (see Fig. 8A, p. 54). In sim- 
ple forms like this, gametes and spores are frequently indistin- 
guishable. The similarity goes even further, as we shall see 
later (p. 133). 

There is, indeed, but one real distinction between spores 
and gametes. The former can begin cell division autono- 
mously if external conditions are favorable; but gametes 
must normally undergo fertilization before cell division and 
development can start. In the gamete, mitotic activity is 
blocked. In the spermatozoon, this might be due simply to 
its lack of cytoplasm and foodstuffs. The ovum, however, has 
no lack of these, and the obstruction must be of another sort. 
Just what, we cannot say, although we do know that it can be 
removed by agents other than the entrance of a sperm. In 
some of the algae and in many animal ova, even in those of 
mammals, development may be activated by a great variety 
of causes. 3 

There is great variety in the time at which this block, the 

3 Salts, acids, alkalies, hypertonic solutions, temperature change, electrical 
stimulation, shaking, puncturing with a needle, are examples. However, 
what works with one egg often will not work with another, even though 
they are closely related. 


occasion of syngamy, occurs with respect to meiosis. As 
meiosis is a consequence of syngamy and cannot be under- 
stood except as a complement to it, we might expect it to 
follow syngamy immediately. This, however, is not so in the 
higher animals and plants, and we have to turn to primitive 
organisms to find such a situation. Although, so far as is 
known, this sequence occurs in only two of the protozoa (a 
sporozoan and a gregarine), it is frequent in the lower plants, 
such as desmids and diatoms, and especially in the conjugat- 
ing algae. In Spirogyra, the familiar filamentous green alga 
with the spiral chloroplast, two strands may often be ob- 
served "conjugating." A bridge of protoplasm forms be- 
tween adjacent cells of the two strands, and the entire sub- 
stance of one cell, cytoplasm as well as nucleus, passes over 
the bridge and merges with that of the other. Then the 
nuclei fuse. This, of course, is syngamy, and a diploid 
nucleus results. The zygote thus formed is set free from the 
filament, and forms a cyst, capable of withstanding unfavor- 
able conditions, such as drought or winter weather. When- 
ever vegetative growth again becomes possible, the cyst 
(zygote) germinates. Its first two divisions are the meiotic 
divisions. Of the four nuclei thus formed (the cytoplasm is 
not divided up), three degenerate. Then, from the cell with 
its one remaining haploid nucleus, there is produced by 
mitotic cell division a typical filament, all the cells of which 
are likewise haploid. 

We have seen that the cycle arising from the act of syngamy 
is: syngamy-^diploid constitution-*meiosis->haploid consti- 
tution^syngamy again. To compare the relative length and 
importance of these alternating diploid and haploid phases of 
the life cycle in Spirogyra, we can best resort to a diagram 

(Fig- 35)- 

In higher plants, the haploid phase gradually gives way to 
the diploid, and intermediate forms exist which have a 
marked alternation of haploid and diploid generations. 
These may be diagramed in a similar way (Fig. 36). In these 




Fig. 35. The relative lengths of the haploid and diploid phases of the life 
cycle in the common green alga Spirogyra. Haploid, thin line; diploid, 
thick line. 

life cycles meiosis takes place just before the formation of 
spores. The diploid plant accordingly produces spores; it is 
the sporophyte. The plant of the haploid generation then 
produces gametes and is called a gametophyte. The diploid 
and haploid plants are usually quite different, so much so, in 
fact, that in one brown alga (Cutler ia A glaozonia) they were 
actually considered different genera until the life cycle was 
worked out. 

Syngamy ^ Syngamy ^ Syngamy \ 

osis I 



famy \ 

>sis I 

Mosses and Liverworts Ferns Seed Plants 

Fig. 36. The relative lengths of the haploid and diploid phases of the life 
cycle in mosses and liverworts (bryophytes), in ferns (pteridophytes), and in 
seed plants (spermatophytes). Haploid, thin line; diploid, thick line. 

However, it is not the alternation of generations of hap- 
loid and diploid multicellular forms that in itself interests us 
here. A comparable alternation does not exist in animals. 
Nor is there any real connection between the vegetative forms 
and the chromosomal constitution. This is known from the 
fact that, by suppressing meiosis, diploid "gametophytes" can 
be produced, and by stimulating unfertilized eggs to develop, 
haploid "sporophytes" can be obtained, in each case the re- 


verse of their normal chromosomal constitution. The impor- 
tant consideration is that this alternation reveals plainly that 
the immediate production of gametes is not the invariable re- 
sult of meiosis. Meiosis produces haploid reproductive cells, 
but these are typically "spores." 

As the importance of the haploid phase is progressively 
diminished from the lower plants to the higher, the gameto- 
phyte is finally reduced to two or three cell divisions para- 
sitically dependent upon the sporophyte. 4 Yet even here 
meiosis does not result directly in the production of gametes. 


Fig. 37. The relative lengths of the haploid and diploid phases of the life 
cycle in animals. Haploid, thin line; diploid, thick line. 

In animals, on the other hand, the gametes are the product 
of meiosis itself. The whole difference between the sexual 
cycle of animals and that of the various plants lies here. Yet 
it is not, after all, more than a minor change, even though it 
results in the restriction of the haploid phase of the life cycle 
to the gametes themselves. A diagram representing the situ- 
ation in animals (Fig. 37) is very much like Fig. 36, which rep- 
resents the situation in the higher plants. 

The production of gametes by the meiotic divisions is the 
result of synchronizing the block to mitotic activity and 
meiosis. Yet even among animals, just as among plants, there 

4 The superiority of diploidy, on account of its insurance against the dele- 
terious effects of mutated genes, has no doubt been a major factor in the evo- 
lution of plant life. The alternation of haploid and diploid generations does 
possess definite evolutionary advantages; but wherever, as in the higher plants, 
there appear in the diploid phase of the life cycle such mechanisms (self-fertili- 
zation; vegetative propagation) as provide the same advantages we find in the 
haploid gametophyte (namely, rapid expression of new recessive mutants and 
breeding true to type), then the gametophyte tends to become vestigial. 


is no exact uniformity in the time at which this block occurs. 
It varies considerably in its incidence; it may fall just before, 
during, or just after meiosis. Table II shows that even among 
closely related types there is no uniformity. 

Table II 

Incidence of block Type of organism 

1. After ovum is mature Higher plants; sea urchins, co- 

elenterates (rare in animals) 

2. During second reduction di- Some invertebrates; many ver- 
vision (at metaphase or ana- tebrates — frog, mouse, bat, 
phase) etc., probably man 

3. During first reduction divi- Many invertebrates (various 
sion (at metaphase) worms, insects, mollusks) 

4. Before reduction Common in invertebrates (var- 

ious mollusks, crustaceans, 

The incidence of the block relative to the meiotic process 
is one of the hereditary characteristics of each particular or- 
ganism. In other words, genetic factors control the time at 
which the block intervenes. This is an important fact, since 
it follows that the alternation of haploid and diploid genera- 
tions characteristic of the plant kingdom and the relative 
absence of a haploid stage in animals are not, as might seem 
at first, fundamentally remote sorts of life cycles. To put it 
another way, a rather simple genetic change, a mutation or 
so, might entirely remove this block to development in the 
reproductive cells formed by a diploid animal, and thereby 
transform these cells from gametes to "spores" and introduce 
a haploid phase into the life cycle. 5 

5 This has actually occurred. In bees, ants, and wasps, and among various 
other invertebrates, eggs may develop without having been fertilized. These 
eggs are, then, equivalent to spores, for they are reproductive cells lacking 
that block to developmental activity which is characteristic of gametes. Like 
the haploid phase of the plant's life cycle, the haploid individuals developing 
from these unfertilized eggs produce gametes which require syngamy. This 
situation, known as haploid parthenogenesis, is linked with the mode of 
sex determination in these insects, so that the haploid individuals are male. 




Formation of 




Oogenesis Spermatogenesis Megagamete Microgamete 






Fig. 38. A comparison of gamete formation in animal and flowering plant. 
For explanation see text, pages 131-133. 


Gamete formation is similar in animals 
and higher plants 

From what has been said, it is clear that the formation of 
the reproductive cells in the higher plants is quite similar to 
that of animals. Figure 38 makes this clear, similar stages be- 
ing placed on the same level, with diploid cells indicated by 
thick lines and haploid by thin lines. 

The first three horizontal rows are evidently alike in all 
four columns. The two cell divisions represented here 
merely indicate that each prospective reproductive cell has a 
lineage which goes back to the diploid zygote formed by 
syngamy, a lineage which, through an indefinite number of 
cell generations, consists of undifferentiated cells. 

We may really start, then, from any single cell in row 3. 
These are the cells which will undergo meiosis. First, how- 
ever, each passes through quite a long period of growth and 
food storage; and here we can notice the first difference be- 
tween our columns. The growth and storage of food are 
greater in the prospective female gametes of both animals and 
seed plants than in the prospective male gametes. Row 4 
shows the products of the first meiotic division. In the male 
lineages the cells which are produced by division are equal 
in size, but in the female lineages one cell receives all of 
the stored food, plastids or other organized cell structures, 
and most of the protoplasm. This is brought about by the 
particular orientation of the spindle. When the spindle lies 
close to the surface of the cell (as it does whenever there are 
present large amounts of inert substances, such as food, which 
impede cytoplasmic division), it makes a great difference 
whether the axis of the spindle is parallel or perpendicular to 
the surface of the cell: for if the spindle is parallel to the sur- 
face, the cell offspring will be equal; but if it is perpendic- 
ular, the outer cell will be very small, and the other, which 
will be very large, will get all the stored substances. Both 
kinds of orientation occur, each in an appropriate situation. 


When, during cleavage of the zygote (see Chapter V, p. 226) 
it is vital for each cell to get its share of the food needed for 
the activities of cell division and development, the spindle 
regularly lies parallel to the surface of the cell. But when, as 
here, the life and growth of a new individual depend upon 
the sufficiency of the food contributed by the ovum, the spin- 
dle is perpendicular, and the stored food supply is not divided 
up (see Fig. 63). As a result, each animal ovum is accom- 
panied by three tiny, functionless polar bodies; and the mega- 
gamete of a flowering plant, typically, by three vestigial mega- 
gametes. On the other hand, in the male lineages each of 
the quartet of haploid cells produced by meiosis is func- 
tional. In animals these differentiate into spermatozoa with- 
out further cell division (Fig. 38, row 5a); in the plant they 
are the pollen grains. 

Figure 38 shows three more cell generations in the female 
lineage (rows 6, 7, 8), and two more cell generations in the 
male lineage (rows 6, 7) of the flowering plant. These rep- 
resent the growth of the vestigial haploid phase of the life 
cycle (the gametophyte). The three divisions of the megaspore 
produce an oval embryo sack of eight cells. Five of these are 
accessory and play no important role. Two nuclei in the 
center remain in an undivided mass of cytoplasm which con- 
tains most of the stored food of the megaspore; these are the 
endosperm nuclei. The eighth cell, at one end, is the mega- 

Within the pollen grain there are produced two micro- 
gametes and one pollen tube nucleus, but the cytoplasm of 
the pollen grain is not divided up. When the pollen grain 
alights upon the stigma of a flower of its own species, it 
commences vigorous growth, forming a pollen tube which 
penetrates the stigma and eventually reaches the embryo sack 
of an ovule. As it grows, the pollen tube nucleus stays at 
the tip; when its work is done it degenerates. The micro- 
gametes also move down the pollen tube as it lengthens and, 
when the embryo sack is reached, penetrate it. Here occurs 


the peculiar fertilization mentioned earlier (p. 62 ftn.), with 
one microgamete fusing with the megagamete to form a 
zygote, the other fusing with the two endosperm nuclei to 
form the triploid endosperm. 

The similarity of spores and gametes is very striking here. 
Spores from each plant cell undergoing meiosis are typically 
produced in groups of four (row 5 in Fig. 38), although by 
a succeeding mitosis or two they may, in some organisms, be 
further increased in number. In animals, gametes are also 
typically formed in quartets, although in a few organisms 
extra divisions multiply their number also. In many plants 
spores are differentiated, like gametes, into large and small, 
the large producing a female haploid plant, and the small, 
a male (row 5, Fig. 38). Moreover, three of the four mega- 
spores in a group generally degenerate and only one is func- 
tional; just as, when each animal ovum is being formed, three 
nonfunctioning polar bodies accompany it (rows 4, 5, Fig. 
38). The transportation of the reproductive cells of the male 
line to the female line occurs in both animals and seed plants 
between rows 5 (5a) and 6. Hence, in the former, gametes 
are transferred; in the latter, spores (pollen grains)— yet an- 
other instance of parallelism. 

In these ways the sexual cycle is superimposed upon the 
reproductive cells. Syngamy removes a block to mitotic activ- 
ity, a block which differentiates gametes from spores. This 
block may be shifted by minor genetic changes. Thus there 
arise forms with alternating haploid and diploid phases of 
various lengths and degrees of importance (higher plants). 
When the block is imposed during meiosis, the entire haploid 
phase is eliminated, except for the gametes themselves, and 
we have the purely diploid individuals characteristic of the 
animal kingdom. 


In all but the very simplest organisms gametes can always 
be distinguished as either male or female. Although among 


lower organisms, such as diatoms and green algae, amebas 
and ciliates, gametes usually cannot be clearly recognized as 
male or female, in many of these the fusing gametes are 
readily distinguishable by differences either in size and form, 
or in activity. In Mucor, a bread mold, for example, all the 
threads look alike. Yet they are different physiologically, for 
not all strands will conjugate; that is, only the gametes of 
certain strands are different. It is, indeed, very questionable 
whether there are any organisms in which fusing gametes are 
both physiologically and morphologically alike. It appears 
probable that the impulse toward syngamy depends upon the 
existence of unlikeness, that the very foundation of sex is an 
affinity of unlike forms. Of course, not too unlike! Male and 
female gametes show decreasing affinity for one another as 
they come from species more and more distantly related. But 
even sperms and ova of different phyla seem to have some 
affinity for one another— for example, those of mussels and sea 

Sexual differentiation can be found even within the most 
closely related cells. Some authorities on the subject main- 
tain that it is a universal phenomenon among sexual organ- 
isms that every individual, and indeed every cell, possesses 
the potentialities of both sexes. 6 

It has been discovered that in the flagellates two "sex sub- 
stances" are given off into the water and may be obtained 
apart from the organisms by filtering them off. It is also 
claimed that these two substances are produced by every 
individual, but that groups of individuals differ in the relative 
proportions of the two substances they secrete. Hence the 
organisms can be grouped into "mating types," individuals 
of one mating type pairing only with others of a not too 

6 Hartmann, Max. Verteilung, Bestimmung, und Vererbung des Ge- 
schlechts bei den Protisten und Thallophyten. "Handbuch der Vererbungs- 
wissenschaft," No. 9. This monograph on sex determination in primitive 
forms of life will undoubtedly prove stimulating to those who can read it. 
Like the other monographs of this most authoritative series, it has, unfor- 
tunately, never been translated into English. 


similar type. In other primitive organisms (fungi, Para- 
mecium) "mating types" have also been discovered. Some- 
times there are only two in any local group, but again there 
may be more. Whether or not we regard the latter situation 
as a multiplicity of sexes, there seems to be ground for believ- 
ing that these differences of mating type are all based upon a 
chemical bipotentiality, so that we may speak of a "male" and 
"female" principle, although perhaps we cannot term par- 
ticular mating types definitely male or female. 

These chemical principles of sexuality that are responsible 
for the act of syngamy are not necessarily identical with those 
which underlie the differentiation of gametes into a large, 
nonmotile female type and a small, active male type. This 
appears to be the case from observations that large "female- 
type" gametes may pair with those of a different mating 
type which are, nevertheless, also large and apparently "fe- 
male" in type. Definitions of sexuality become exceedingly 
controversial when applied to primitive forms. We can only 
reach agreement upon the application of the terms male and 
female wherever the mating types are reduced or limited to 
two and where these produce mega- and microgametes, 

Among all definitely sexual species, a second sort of bi- 
potentiality appears to be a fundamental characteristic; that 
is, the capacity to produce both male and female gametes 
is present in each individual, although it may not be de- 
veloped or exercised equally. This is evident in the great 
majority of plants and is well-nigh universal among the more 
primitive ones. The lower animals, too, are nearly all her- 
maphroditic; and among those more specialized types char- 
acterized by isolated sexes, such as insects and mammals, inter- 
sexuality and sex reversal are sufficiently frequent to impel 
us to believe that bipotentiality is a rule there, too. 

Whether we are dealing with the first or the second type 
of sexual bipotentiality, we can safely assume that either is 
due to genetic factors, just as we assume that these underlie 


all developmental potentialities; and we may symbolize them 
by letters, keeping in mind, however, that they probably 
represent gene complexes rather than single genes. Letting 
M represent the potentiality for maleness and F that for 
femaleness, the basic genotype as to sex is then MF when 
haploid, MMFF when diploid. 

Most evolution has tended to increase the organism's con- 
trol over its own internal environment— over its basic life- 
processes. The ultimate step in this direction is to superim- 
pose the internal, stable biological control provided by genes 
upon the haphazard, less easily regulated determination by 
the environment. Sex being one of the basic life phenomena, 
it is not surprising that, in the course of organic evolution, 
genetic factors have arisen which react with, or even replace, 
nongenetic ones in controlling the time and mode of sex 

First there seem to have been established genes control- 
ling the incidence of sex determination (that is, its time in 
the life cycle and its place within the organism); for in a 
great many animals and plants this is all that has ever de- 
veloped. Occasionally the determination of which cell or 
group of cells shall be male and which shall be female is left 
largely to the mercies of the external environment. For ex- 
ample, most larvae of Bonellia, a marine worm, when isolated 
become females; but a larva that finds a female becomes 
attached to her proboscis, develops there into a tiny, parasitic 
male, and ultimately lives within the female's uterus. In the 
horsetail (Equisetum), strong light and plenty of nutriment 
lead to the development of exclusively female sex organs, 
while the lack of these environmental factors results in male 
sex organs. In other plants certain soil conditions tend to 
exert a similar sex-determining effect. 

However, like other developmental traits, sex is generally 
controlled through the internal environment by the action 
of certain parts of the organism upon other parts. The little 
moss Funaria affords us a relatively simple example of this 


situation. Each haploid spore of Funaria germinates into a 
plant with two branches, one apical, the other lateral. The 
apical branch is always male, the side branch female, while 
the stalk on which they grow is neuter. Now, the differentia- 
tion of the one branch as male and the other as female is, no 
doubt, a matter of reciprocal relations; but the fixation of the 
time and place at the moment of branching is a species char- 
acteristic, hereditary, and, we therefore assume, genie. 7 

In Funaria sex differentiates in the course of the haploid 
phase. The diploid plant which grows from the zygote is, 
like the haploid plant in early growth, sexually bipotential 
and neuter. Many ferns and mosses are like Funaria in this 
respect. On the other hand, if genes impel sex to differentiate 
at some time during the diploid phase, the differentiation 
then persists through the haploid phase, too. Among plants 
the higher ferns and a large majority of the flowering seed 
plants, and among animals the coelenterates, flatworms, and 
annelids all fall into this group. This situation is probably 
the most universal in respect to sex. 

Considering plants first, we find that many, such as the pea 
and the bean, the rose and the lily, have flowers which contain 
both male and female organs, the stamens and the pistils, re- 
spectively. Here sex makes its appearance during the forma- 
tion of the flower. Next there are a few plants, such as the 
horse chestnut, which have some flowers mixed, some pure. 
The horse chestnut, for instance, has mixed flowers and pure 
male flowers on the same tree, so that sex becomes differen- 

7 It is not at all plausible that most fundamental inherited characteristics of 
a species are nongenic, and that minor variations monopolize the most 
effective means of cellular division, mitosis. There is a good reason why we 
cannot prove the genie nature of the major characteristics of any given form 
of life. Because they are so vital a feature, any change in the genes govern- 
ing them is almost certain to lead to a condition that will be lethal during 
development; such mutations are immediately eliminated. These genes are 
consequently kept homozygous. But through meiosis and syngamy we are able 
to trace only heterozygous pairs of genes. We are dependent upon differences 
between alleles for our knowledge of each specific gene. It is, therefore, quite 
probable that we shall never be able to identify many of those which are most 


tiated sometimes during flower formation and sometimes just 
before. (However, each plant species is quite constant in the 
kinds of flowers a single plant will bear.) Transitional forms 
such as these lead us to a type where the flowers on a plant 
are all either pure male or pure female, though both grow 
on the same plant. This condition is probably as familiar 
to us as the first— think, for example, of the squash and cu- 
cumber, maize, chestnut, beech, and birch. 

In hermaphroditic animals, sex is usually distinguishable 
only in the sex organs. These are often present simultane- 
ously, as in the earthworm; in other forms, such as the com- 
mon Hydra, they are not present together, except rarely, but 
arise at different seasons. 

Sex differentiation may thus fall early or late in the dip- 
loid, as well as in the haploid, phase. The very fact that it 
may occur during the phase shows that it is not a phenomenon 
of chromosome segregation, which occurs only at meiosis. The 
genes determining its time and place must normally, therefore, 
be homozygous— and in this respect sex differentiation is no 
different from that of any other developmental trait (see 
Chapter V). To portray the situation we may, then, represent 
the genotype of the sex-gene complexes as MFZ in the hap- 
loid phase and MMFFZZ in the diploid, letting Z stand for 
those genes which fix a characteristic time and place for sex 
differentiation in each species or variety. This may be ex- 
pressed in a diagrammatic way (Fig. 39) in connection with 
the haploid-diploid life cycle. The genes represented by Z 
may be envisaged as the alarm hand of a clock, pointing to the 
time in the cycle when sex is realized— when, if haploid, MF 
becomes (M)F and M(F) in different parts of the body, or, 
if diploid, MMFF similarly becomes (MM)FF and MM(FF). 


Complete isolation of maleness and femaleness appears to 
have arisen from hermaphroditism. In some plants, in many 



invertebrates, and even in some fishes, sexuality is consecu- 
tive or alternating. In some of these forms the individual 
first passes through a functional male phase, next matures as 
a female, and then may revert to a final condition of male- 
ness, or, like the common oyster, may continue to vary back 
and forth with the seasons. The same primitive germ cells 

Sex Determination 
in the 


-Diploid Phase 

Syngamy ^ Meiosis 



+ ^Diploid 

Fig. 39. Sex determination in the haploid phase, as in the moss Funaria, con- 
trasted with sex determination in the diploid phase, as in maize (Zea). 
$ rz sexually undetermined; $ — : male; $ =: female. M, genes for male- 
ness; F, genes for femaleness; Z, genes controlling the time and place of sex 
determination in the life cycle. The "alarm hand" indicates the time at which 
sex is determined. The symbols for the M and F genes whose effect is locally 
and temporarily inhibited are placed in parentheses. 

are able to develop either into sperms or into eggs, depend- 
ing upon the sexuality of the reproductive organs, and dur- 
ing the course of sex reversal self-fertilization may even occur. 
In other forms, such as Crepidula, a marine snail, the fe- 
male phase, once it is attained, persists throughout life. Since 
male and female gametes do not mature together during sex 
reversal, self-fertilization is prohibited. Here, then, in con- 
trast to the preceding instances of but partial isolation of the 
sexes, functional maleness and femaleness do not coexist in 
the same individual. Like change of plumage in a fowl from 


an immature to a mature phase or like metamorphosis in in- 
sect and amphibian, this consecutive type of sexuality is gov- 
erned by homozygous genes, in the manner described in the 
preceding section. 

However, most organisms have hit upon a simpler mecha- 
nism for bringing about the isolation of maleness and female- 
ness. Not only can sex be determined by genes acting either 
during the haploid or during the diploid phase of the life 
cycle, but it can also be determined at the time of change from 
one phase to another, that is, at meiosis or at syngamy. This 
latter situation, of particular importance among the higher 
animals, has far-reaching effects. It brings about, besides the 
isolation of maleness and femaleness in separate individuals, 
the inheritance of nonsexual traits in association with sex, 
and a maintenance of the sexes in an approximately equal 
ratio. Let us see how this is brought about. 

In the first place, if sex determination falls at meiosis, the 
sexes will, as a consequence, be isolated throughout the en- 
tire following phase; that is to say, haploid individuals will 
be male or female and not neuter or of mingled sex. This 
is true of certain ferns. 

If, on the other hand, sex is determined at syngamy, isola- 
tion is complete for the whole diploid phase and carries over 
through the entire succeeding haploid phase as well. Among 
the seaweeds of the genus Codium, we may trace the evolu- 
tion of such a step. There is one species (C. decorticatum), the 
diploid plants of which bear both male and female sex organs. 
In another member of the group (C. elongation), both kinds 
of sex organs grow sometimes on the same plant, at other 
times on different plants, apparently depending upon the 
season of the year. In yet other relatives, male and female sex 
organs grow only on different plants; that is, the sexes are 
quite isolated from the time of syngamy on. Another ex- 
ample, in a more familiar organism, is found in maize. Sev- 
eral mutant genes have been found which in combination can 


convert the normally monoecious 8 Indian corn into a type 
with isolated sexes (see p. 145). 

The determination of sex at meiosis or syngamy may be 
brought about environmentally, as in C. elongatum, but in 
most known cases it is genetic. We might indicate this in 
Fig. 39 merely by shifting the "alarm hand," representing 
the action of genes which fix the time of sex determination, 
until it points either to meiosis or to syngamy. However, 
such genes are rarely homozygous. They are, as a rule, heter- 
ozygous, and sex is determined by their segregation and 

Before we go on to trace this behavior, it will be well to 
ponder for a moment the significance of the separation of 
maleness and femaleness. From childhood we are acquainted 
with the fact that they are completely isolated among all the 
higher animals, while, on the other hand, this isolation is 
comparatively rare among the higher plants. What are the 
consequences of these opposed systems, both of which are ap- 
parently so successful, so widespread? 

An isolation of the sexes obviously makes the closest kind 
of inbreeding, self-fertilization, impossible. The converse sit- 
uation permits it. Our question, then, resolves itself into 
the relative genetic and evolutionary merits of inbreeding 
and outbreeding. What reasons lie back of the almost uni- 
versal prohibition of brother-sister marriages among human 
societies? Why does a stockman, on the other hand, con- 
stantly use this very type of cross, or the even closer one of 
parent with offspring, when he wishes to breed a choice variety? 
Among plants with perfect flowers, which are presumably 
capable of self-fertilization, why is there so widespread a 
dependence upon winds and insects to insure cross-fertiliza- 

8 Monoecious and hermaphroditic are the two terms used, respectively, by 
botanists and zoologists to describe the production of both male and female 
gametes by a single individual. Dioecious is the only term describing the 
complete isolation of these sexual capacities in distinctly male or female 


tion? Is there any reason for us to frown upon cousin mar- 
riages? Is there any biological justification for the elaborate 
totem system of the northwestern Indians, which insured 
their marrying outside their own clan? Is it equally good, 
better, or worse, to marry always within the "family" or the 
native village? 

To answer these questions, we must probe the genetic ef- 
fects of self-fertilization. A homozygous individual, AABB, 
will form only AB gametes, and, if self-fertilizing, only AABB 
homozygotes like the parent can be produced. A heterozygous 
AaBb individual forms, as we have seen (Chapter II, pp. 98 ff.), 
four types of gametes. Upon self-fertilization, these will pro- 
duce nine genotypes in various proportions. Four (AABB, 
aabb, A Abb, and aaBB) are homozygous, and, when self- 
fertilized, w T ill breed true. Assuming random assortment 
these will on the average make up one fourth of the progeny. 
One half of the offspring are homozygous for one gene pair, 
but heterozygous for the other. These, when self-fertilized, 
will yield one half homozygotes, one half heterozygotes for 
one pair of genes. The remaining one fourth of the original 
progeny are, like the parent, heterozygous for both pairs of 
genes, and when self-fertilized, will give once again one 
fourth homozygous, one half homozygous-heterozygous, one 
fourth heterozygous. Summing up, at the end of one genera- 
tion of inbreeding, one fourth of the group are completely 
homozygous. At the end of a second generation the propor- 
tion is 14 + (i/ 2 of l/ 2 ) + (14 of 14) = 9/16. We can similarly 
calculate that at the end of a third generation it will be 
9/16 + (l/ 2 of i/ 4 ) + (l/ 2 of l/ 8 ) + (l/ 4 of 1/16) = 49/64. 
Without carrying this farther, one can readily see that in- 
breeding very rapidly reduces a heterozygous group to the 
homozygous condition. Self-fertilization, being the closest 
form of inbreeding, merely does rapidly what other forms of 
inbreeding, such as brother-sister matings and cousin mar- 
riages, do more slowly. 

Our many questions have thus been resolved into a single 


one: Which is better, heterozygosity or homozygosity? The 
answer, of course, must depend upon the nature of the re- 
cessive genes present in the ancestor to begin with. If there 
were numerous beneficial ones and none markedly dele- 
terious, inbreeding, by rendering them homozygous and 
contributory to the phenotype, would unquestionably be 
beneficial. Moreover, once an advantageous phenotype is 
obtained, it will breed true if it is homozygous and is in- 
bred. Thus peas and beans maintain excellent stock by self- 
fertilization— homozygous lines of poor character having all 
been eliminated through selection. Thus, too, the Ptolemies 
of Egypt kept their fine line from deteriorating by brother- 
sister marriages, which produced the most enlightened rulers 
of their time, until, in Cleopatra, the dynasty ended with 
the most brilliant flower of all. 

On the other hand, inbreeding renders homozygous all 
harmful recessive genes, too. The general prevalence of 
these can be recognized if we recall that most mutations are 
recessive, and that of these almost all are detrimental to 
some degree. Deleterious recessive genes are eliminated only 
very slowly by natural selection, and thus close relatives 
tend to carry them in common. This can be seen from 
the fact that the percentage of stillbirths and abortions in 
first-cousin marriages is far higher than in the general popu- 
lation, a situation due to recessive lethal genes being carried 
by both parents (see Fig. 14). 

On the whole, inbreeding results in a merciless weeding 
out of harmful recessive genes. Populations which habitually 
inbreed have been purged. On the other hand, those which 
habitually crossbreed will not have been purged. Individuals 
in them must usually be heterozygous for harmful recessives; 
and inbreeding will, therefore, as a rule result in the emer- 
gence of the undesirable traits. The isolation of the sexes in 
distinct individuals merely prevents that closest form of 
inbreeding, self-fertilization. Since its advantage lies in pre- 
venting the emergence of harmful recessive traits, it probably 


arose in evolutionary lines in which crossbreeding was al- 
ready established and these deleterious traits were relatively 

Having now examined the consequences of an isolation 
of the sexes in distinct individuals,, we may turn next to 
the mechanism by which the isolation is brought about. If 
a pair of genes determining sex was heterozygous, one gene 
favoring maleness and its allele favoring femaleness, they 
would, of course, segregate at meiosis. The resulting haploid 
cells, carrying one or the other, would then be either male or 
female. To our diagram (Fig. 39, p. 139) we need onl y add 
such a gene pair, X favoring F (femaleness), Y favoring M 

Sex Determination at Meiosis 



$ M(F)ZY 

(M)FZX $ 

At syngamy, a male gamete and a female gamete of these 
two genotypes will unite, and the zygote is again hetero- 
zygous for X and Y. As when other alleles interact, the 

phenotype resulting here from the interaction of X and Y 
might be a blend, or one might be dominant over the other. 
Among protozoa, algae, fungi, and mosses, for instance, there 



is generally a blending of the two, and the diploid phase 
is of a ' mixed-sexedness." In a liverwort, Sphaerocarpus, 
however, the allele for femaleness is dominant, and hence 
the sporophyte is female. 

Maize stocks with mutant genes capable of isolating the 
sexes represent another instance of this sort. One of these 
genes, barren-stalk (ba), a recessive, suppresses the develop- 
ment of ears, that is, of the female flowers. The tassel-seed 
(Ts) mutants (there are several, either dominant or recessive) 
convert the tassels, normally male flowers, into female ones. 
Thus a race segregating for dominant tassel-seed but homo- 
zygous for barren-stalk has separate male and female plants. 
The female (Ts/+; ba/ba) produces two kinds of gametes 
(Ts; ba and +; ba). The male (+/+; ba/ba) produces only 
gametes carrying +; ba: The sex of each individual of the 
next generation is then determined at syngamy by its geno- 
type, which will depend upon the kind of egg being ferti- 
lized. Using Y for the recessive male sex gene and X foi 
the dominant female sex gene (tassel-seed), we may diagram 
the situation as follows: 

Sex Determination at Syngamy 
9 X 



Eggs (MFZX) (MFZY) ( gizY) Sperms 

The systems of sex determination we have just described 
will work efficiently only on one condition: There must be 
no multiplicity of such heterozygous sex genes as X and Y, 
for not only does meiosis bring about the segregation of al- 


leles, it also leads to the recombination of genes of different 
pairs. Random assortment of two pairs of sex genes would 
lead to four haploid combinations, or ''sexes," and with each 
added pair the number would increase according to our now 
familiar formula, 2 n . Just such a sexual melange seems to have 
arisen in the common black molds, many of which, apparently, 
have quite a number of "sexes." Only if all the sex-determin- 
ing genes were in one pair of chromosomes (and if crossing 
over were also inhibited) could confusion be avoided. This 
solution to the problem seems to have been discovered more 
than once, and in some of the liverworts sex chromosomes 
(carrying these sex-determining genes) can actually be dis- 
tinguished. Among the pairs of chromosomes, there is one 
made up of two different members. Sometimes one chromo- 
some is a little smaller than its homologue, sometimes a 
great deal smaller, sometimes missing altogether. The hap- 
loid plants getting the large chromosome (commonly called 
the X-chromosome) are female; those getting the little homo- 
logue (the so-called Y-chromosome), or no homologue at all, 
are male. 

Yet even these steps cannot guard against the greatest 
danger to the sex-determining mechanism— that of mutation. 
As long as a single pair of genes bears the entire responsi- 
bility for the regularity of sex determination, any mutation 
of the sex alleles might be fatal. Nor would the danger be 
limited to mutation of the existing sex genes. Mutation 
might give rise even more probably to other genes also having 
a sex-determining potency. Consider the state of the true- 
breeding bisexual (dioecious) maize race we have just de- 
scribed if a recessive tassel-seed mutant were also to arise in 
it and begin segregating! 

Actually the situation here is of little importance to us, 
for it is not widespread. Nor is it likely that it was actually 
a step, unless a very transitory one, in the evolution of sex 
determination in the higher plants and animals. It most 
likely represents an evolutionary offshoot. Logically, how- 


ever, its relative simplicity makes it easier for us to under- 
stand the more complex, yet similar, phenomena of our own 
mechanism of sex determination. 




In the higher organisms there is a multiplicity of sex-deter- 
mining genes, apparently scattered haphazardly among the 
various chromosomes. No doubt this is a consequence of the 
random nature* of the evolutionary processes affecting the 
genes and chromosomes— mutation, translocation, and so 
forth. Since each diploid individual originates through syn- 
gamy, its sex must be affected more immediately by re- 
combination than by segregation. Recombination following 
segregation, however, leads to a multiplicity of combina- 
tions, whereas two sexes are quite enough. How can this 
be avoided? 

If we examine the chromosomes of males and females of 
some one of the higher animals, say, for example, a bug 
(Lygaeus) or a fruit fly (Drosophila). or, for that matter, a 
man, we can get an inkling of the answer. (Because Dro- 
sophila has the lowest number of chromosomes, it provides 
the simplest diagrams.) Drosophila females have four pairs 
of chromosomes, each pair made up of identical-looking 
homologues. In males, however, one of the pairs is com- 
posed of two obviously unlike mates. One of these, rodlike, 
corresponds to one of the pairs present in females; the other is 
shorter and hooked, like the letter / (Fig. 40). Following 
meiosis, all the eggs will carry similar sets of chromosomes, 
but the sperms will be of two kinds, some carrying the straight 
member of the differentiated pair (this one is the X-chromo- 
some), and others carrying the hooked member of the pair 
(this one is the Y-chromosome). Syngamy will then result in 
two sorts of individuals, determined by the type of sperm 





Eggs Spi 

Fig. 40. Chromosomes of female and male Drosophila melanogaster, diploid; 
and of the haploid eggs and sperms. Note that the sperms are of two kinds, 
those with an X-chromosome and those with a Y-chromosome. X-chromo- 
some, solid black; Y-chromosome, shaded; other chromosomes, outline. 

taking part. Since all the eggs carry an X-chromosome, 
sperms carrying an X-chromosome will produce a zygote with 
two X-chromosomes. This will be a female. On the other 
hand, a sperm carrying a Y-chromosome will produce a zy- 
gote with an X- and a Y-chromosome, and such an individual 
will be a male (Fig. 41). 

Female Male 

Fig. 41. Diagram showing how the male and female chromosomal constitu- 
tions are determined at syngamy by the kind of sperm taking part in 

In man, too, females have an XX- and males an XY-consti- 
tution. Here the X- and Y-chromosomes are not distinguish- 
able by shape so much as by size. The Y is a great deal 
smaller than the X, and is, in fact, the smallest of all the 


forty-eight chromosomes. Because we have so many chromo- 
somes (and many of them are extremely tiny), trying to see 
and distinguish the X- and Y-chromosomes in a crowded 
nucleus is similar to hunting for a needle in a haystack. 
However, a number of cytologists have patiently sorted all 
the human chromosomes into pairs; and when these are ar- 
ranged in parallel rows, one for the male and one for the 
female, the XY-pair in the male is obvious enough (Fig. 42). 

U o? o (rfrcitt»»ii>»ow»»iM««i<«H«Hii* 

(f> C? r>) 9> (C Tr « J) » (I <l » » e« « »«et>j»|c»»»>i 

Fig. 42. The forty-eight human chromosomes paired and arranged in order 
of size. The three top rows are from male cells, the first row being from a 
cell of the germ line, the second row from a meiotic cell with homologous 
chromosomes in synapsis (hence there appears to be only the haploid num- 
ber), the third row from a somatic cell. The X- and Y-chromosome pair is 
placed at the extreme right of each row, the Y-chromosome being the ex- 
tremely small one. The bottom row is from a female somatic cell, no such 
unequal pair of chromosomes being evident. Magnified about 1600 diameters. 
(From Painter, after Evans and Swezy. Courtesy of the Journal of Heredity) 

In the fruit fly the Y-chromosome, in comparison with the 
X, is fairly large, whereas in man it is very small. In some 
bugs, such as Protenor, unlike the type previously mentioned, 
it is lacking altogether. These female bugs have two large 
X's, but the males have only one. Sex, nevertheless, is deter- 
mined in exactly the same way in these bugs as in fruit fly or 
man. Two kinds of sperms are formed, one kind carrying an 
X, the other lacking it, and hence having one less chromo- 
some in all. At syngamy, X + X yields a female; X -f- O, a 

The determination of sex by a specific pair of chromosomes 
seems to parallel that which takes place in liverworts, but 



the genetic situation is actually far different. First of all, 
in the higher animals the odd chromosome, or Y, which oc- 
curs only in one of the sexes, may be large or small or even 
entirely absent without any change in the nature of sex de- 
termination. This fact is itself suggestive. Perhaps the Y- 
chromosome has nothing to do with sex determination here! 
We can test this idea by observing those occasional meiotic 
accidents when homologous chromosomes fail to disjoin. 
Such an accident, known as nondisjunction, may befall the 
X-chromosomes in the germ cells of a female, and would 
lead to two kinds of eggs. One would contain two X-chro- 
mosomes, the other none. In the normal course of events 
these would be fertilized by sperms carrying either an X- 
or a Y-chromosome. Drosophila again supplies us with the 
facts. The resulting types, as we can see from Fig. 43, are four 
in number. Neglecting for the moment the other chromo- 

Nbn, disjunction of 
X- Chromosomes 



1,3 ^— ^ %1* ?> 3 

super- o. 9 o* 

Fig. 43. The effects of nondisjunction in a female Drosophila melanogaster. 
Union of kind of egg No. 1 with kind of sperm No. 3 produces a three-X 
super-female, sterile; egg No. 1 with sperm No. 4 produces a normal female 
with an extra Y-chromosome; egg No. 2 with sperm No. 3 produces a normal- 
appearing, sterile male; egg No. 2 with sperm No. 4 yields a type without an 
X-chromosome that perishes early. 


somes, all handed down quite as usual, we can describe these 
four types by their X- and Y-chromosome constitution. The 
first has three X's; the second, two X's and a Y; the third, one 
X; and the fourth, a Y. Now what sex have these combina- 
tions? Two, the second and third, turn out to be perfectly 
normal-seeming females and males. In other words, two X's 
and a Y have the same effect in determining sex as two X's 
alone, while a single X has the same effect as an X plus a Y. 
This amounts to saying that the Y-chromosome has no sex- 
determining effect. It is not truly a sex chromosome. The 
X's are the sex chromosomes, two X's producing a female, 
one X a male. 9 

These facts prove the responsibility of the X-chromosome 
for determining sex, but the question of the number of sex 
genes the X carries still remains. Many years of experiment 
and controversy elapsed before it was shown that there was no 
single major sex gene in the X-chromosome, but that numer- 
ous well-scattered genes in it act cumulatively in determining 
sex. This fact was demonstrated by a study of the effects 
upon sex of each one of a number of short successive seg- 
ments of the X-chromosome, both in excess and in deficiency. 
Reliance upon many sex determinants rather than upon a 
single pair must frequently have proved itself good insur- 
ance against any disturbance of the system introduced by 
mutation. Combining this advantage with that providing 
for the segregation and recombination of an entire set of 
sex genes as a unit has achieved remarkable efficiency and 
durability for this, the prevalent mode of sex determination. 

The sex genes of the X-chromosome are evidently female 
in effect. Where, then, in these diploid organisms with iso- 
lated sexes, such as the fly or man, are the male determinants? 

9 The no-X type perishes while still an egg. It is unable to take even the 
first few steps in development. Flies with three X's do somewhat better, al- 
though none too well. If their environment is optimum in every respect, as 
many as half of them may succeed in passing the perils of pupation and in 
crawling out into adulthood, sterile weaklings with all sorts of defects. (They 
are called by geneticists super-females, but that certainly cannot mean a supe- 
rior expression of feminine traits!) 


Is the number of X-chromosomes the sole factor? Is a fe- 
male just two doses of maleness? Or, turning it round, is a 
man, so to speak, but half a woman? This would be one 
way of explaining the situation just presented. A final experi- 
ment yields an answer. 

Sometimes, though very rarely, of course, nondisjunction 
will involve, besides the sex chromosomes, all other pairs 


Fig. 44. The production of a triploid female through the union of a diploid 
egg and a haploid sperm (Drosophila melanogaster). 

as well. In this way we may obtain an egg with a full diploid 
quota of chromosomes. Fertilized by an ordinary sperm 
carrying an X, an individual will arise with three of each 
kind of chromosome, a triploid (Fig. 44). Now this triploid is 
a perfectly vigorous, fertile female, although, like the super- 
female, it has three sex chromosomes. What is the difference? 
It can be only that the other chromosomes, the autosomes, 
as they are called, are triploid too. But this must mean that 
the autosomes, as well as the sex chromosomes, have to do 
with sex determination. To summarize, using A to stand for 
a haploid set of autosomes: 

2X + 2A = $ and 3X + 3A = $ ; but 
X + 2A = $ , while 3X -f 2A = super-female. 

This suggests that maleness and femaleness here depend on 
a particular balance or ratio between genes in the X-chromo- 
some and opposing genes in the autosomes. Since, with a 
given set of autosomes, a cumulation of X's (from X to 2X) 
tends from maleness toward femaleness, we can say that the 


sex genes of the X-chromosome tend toward femaleness, and 
those of the autosomes tend toward maleness. 

This concept is further strengthened by observing what 
happens when a diploid egg, like the above, is fertilized by 
the type of sperm which carries a Y-chromosome instead of 
an X. The resulting individual would have two X-chromo- 
somes (plus a Y), and three full sets of autosomes, that is, 
2 X + 3A. If 3X + 3A is a female, we might expect 2X + 3A 
to be something less than a female; and, since the male ratio 
is 1X : 2 A, we might expect 2X + 3 A to be something more 
than a male. This expectation is realized in fact. The 2X + 
3A individuals are a peculiar type, with some characteristics 
of each sex. They are sterile intersexes. They usually re- 
semble females somewhat more than males. 

What an ingenious system is this that determines the 
sex of a diploid individual in spite of a multiplicity of sex 
genes, simply through the segregation of chromosomes at 
meiosis and their recombination at syngamy. One particular 
pair of chromosomes has become the sexual counterpoise of 
all the others; and this one particular pair has further be- 
come haploid in one sex and diploid in the other. Through 
segregation, individuals haploid for this chromosome pro- 
duce two kinds of gametes; individuals diploid for it, only 
one. Hence there are produced at fertilization only two com- 
binations, the female with two such chromosomes, the male 
with only one. In Fig. 45, this system is added to the more 
fundamental sex system, upon which it is superimposed. 

In this way, then, sex is predetermined from the very in- 
stant of fertilization, along with the remainder of the hered- 
itary pattern. Away with all superstitions that by thinking 
this or doing that we can determine the sex of our yet un- 
born children! What good to hope or dream or pray? Before 
growth and development ever commence, through the ran- 
dom chance of this or that sperm's arrival first at the egg, 
the genie combination is produced which will favor the ex- 
pression of one of the two sexual potentialities. 







$ ~'~ d 

Fig. 45. Scheme showing the sex gene system of a form, like Drosophila or 
man, in which the male sex-determining genes (M) and some of the female 
sex-determining genes (F) are always homozygous, while other female sex- 
determining genes (X) are diploid in one sex, haploid in the other. The sym- 
bols for the sex genes whose effects are temporarily inhibited are placed in 

If we would ourselves control sex determination, we must 
first learn how to distinguish the two kinds of sperms and 
then how to separate them effectively. Although we may 
ultimately succeed— and there are those who claim to have 
detected a bimodal distribution of sperm size or weight— it 
remains as yet impossible to separate them. 

Through the mechanism of meiosis, that is, through the 
segregation of X- and Y-chromosomes, female-producing 
sperms carrying an X, and male-producing sperms carrying 
a Y, are formed in equal numbers. A direct result is the 
numerical equality of the two sexes in a population. Birth 
statistics show us, however, that this equality of the sexes is 
only approximate. For every 100 girl babies born, there 
are on the average 105 boy babies. To what can this upset of 
the ratio be due? We think at once of the possibility of selec- 
tive mortality during the prenatal period. Perhaps more 
girl babies die before or at birth. The doctors can tell us 


something about this. "In the United Kingdom, the pro- 
portion of male to female deaths before birth is about 150 
to 100; for still-births it is 135 to 100. . . . And just the same 
happens in other mammals, such as cattle." 10 Astonishing! 
Meiosis results in equal numbers of male-producing and 
female-producing sperms, more male embryos die before 
birth, more die at birth, and still there are 105 males to every 
100 females. If we take these deaths into account, there must 
be about 120 males conceived to every 100 females. "This 
... can only be accounted for by some advantage possessed 
by Y-bearing sperms which enables them to fertilize more 
eggs than their X-bearing brethren. Presumably the male- 
producers have greater powers of endurance than the female- 
producers and can better withstand the arduous journey up 
the uterus and oviducts. We may guess from the statistics 
that for every six male-producers only five female-producers 
get to the top of the oviduct; that six out of every eleven 
among the millions that lose themselves and perish on the 
way are female-producers." n 

Before passing on to quite another subject, one more 
word should be said about sex determination. The final type 
which we have just described is, indeed, that commonest 
among the higher animals, and it holds surpassing interest 
for us as the method whereby sex is determined in our own 
species; but it is after all only one of several. In describing 
the system, for example, it was said that one particular pair 
of chromosomes has become the sexual counterpoise of all 
the others. Now would it not seem as likely that this particu- 
lar pair should carry the male-determining as the female- 
determining gene complex? If so, the situation would be 
quite reversed, XX producing a male, and XY (or XO) a 

10 Wells, H. G., Huxley, Julian, and Wells, G. P. The Science of Life, p. 
555. Doubleday, Doran, New York, 1931. Praise need scarcely be given to 
this comprehensive attempt to provide for the layman an understanding of 
the facts and values of biology. This quotation and the following speak for 
themselves, indicating both the individual and the social points of view de- 
veloped, and the clear and appealing style. 

11 Ibid., p. 557. 


female. 12 The sperms would then all be alike, and the eggs 
would be of two sorts, destined to become either males or fe- 
males. In the long evolution of animal life, this converse 
type of sex determination has arisen several times, for it is 
characteristic of two very unlike groups, the birds, and the 
moths and butterflies. It is also to be found in some of the 
fishes, where even closely related species differ as to which 
sex is heterogametic (XY, or XO). 

Another change in the system, perhaps of a common sort, 
has been found in the gypsy moth (Lymantria dispar). In 
this species the sexual counterpoise to the determinants in the 
sex chromosomes has been located in either the Y-chromosome 
or the cytoplasm instead of in the autosomes. 13 Since the egg 
alone contributes the Y and the cytoplasm to the offspring, 
this sex determinant, F, is transmitted through the female line, 
from mother to daughter. Numerous geographical races of 
this moth can be bred together, but then produce some inter- 
sexual offspring. These intersexes are not like those of Dro- 
sophila, which resulted from nondisjunction, for they have 
a normal diploid quota of chromosomes, and are either XX 
or XY in sex-chromosome make-up. Their intersexuality 
must therefore be due to a difference in the strengths of the sex 
determinants. Within any single race, M and F are so counter- 
poised that two Ms and an F produce a male, but one M and 
an F produce a female. If the strengths of the M's (or F's) of 
two races fail to correspond, the delicate balance is disturbed 
in their offspring, and an intersex results. Even within this 
single species a number of M's and F's of differing strength 
have arisen, whether by mutation, by recombination, or by 
some other kind of change. It is quite likely that much of the 
sterility of interspecific hybrids has been produced in a sim- 

12 in order to avoid confusion with the type in which the male is the 
heterogametic sex, some geneticists prefer to use the symbols ZZ and ZW for 
XX and XY, when the female is heterogametic. 

13 This raises the whole problem, which we have so far disregarded, of the 
existence of hereditary factors not located in the chromosomes. Very few are 
known, and these occur mostly among the plants. The topic can be treated 
better in Chap. IV. 


ilar fashion, for in Drosophila, too, research has shown that 
numerous genes are responsible for the intersterility of two 
races of the same species (D. pseudoobscura). 

In the gypsy moth the evolution of the sex-determining 
mechanism appears to be still in progress. This evolution be- 
gan with sexual bipotentiality; upon this foundation was su- 
perimposed the control of modifying genes, first, no doubt, 
simply haploid, meiotic; then came the more complex balance 
of male and female determinants and the appearance of the sex 
chromosomes, diploid in one sex, haploid in the other, which 
fix sex at syngamy, at the very beginning of the diploid phase 
of life. In the main line of evolution among animals the 
male has remained the heterogametic sex. But several times 
there has been a switch to the female, once in the evolution 
of the insects, one or more times in that of the modern bony 
fishes, and again at the time when birds diverged from the 
ancestral reptilian stock. Within each isolated population, 
alterations in the sexual mechanism have taken place so that 
interbreeding with related populations, whenever the isola- 
tion breaks down, is more and more restricted. Sexual isola- 
tion adds its effect to other forms of isolation, and the in- 
cipient species diverge more than ever. This we can see 
still going on in modern organisms, for the evolution of sex 
is not ended. Had it been possible for some human race, 
such as the Pygmies of Central Africa, to maintain its isola- 
tion a few thousands of generations longer, we might perhaps 
have seen it shut off from us forever through barriers of 
intersterility more potent than those of ocean, desert, and 


The sexual mechanism prevalent among the higher ani- 
mals has important consequences in the hereditary pattern, 
consequences we should not overlook. These result from the 


inheritance of genes, other than those affecting sex, in the 
sex chromosomes— and we may include the Y-chromosome, 

Genes in the X-chromosome are "sex-linked." This does 
not mean that they are limited to a particular sex, but that 
they follow the X in its distribution. This is not their only 
peculiarity. There is another, a unique thing to be taken 
into consideration. 

Most of the genes in the X-chromosome have no alleles 
in the Y-chromosome. In fact, if we may generalize from 
what we know is true in the fruit fly, there are very few genes 
of any sort in the Y-chromosome. It is little more than a 
dummy! The genes in the X-chromosome of the XY male 
are consequently haploid, and dominants and recessives alike 
will exert their effect without modification by alleles. 

Although our X-chromosomes are by no means the largest 
we have (they come about two thirds of the way down the 
scale of size among our twenty-four pairs; see Fig. 42), more 
human genes have been detected in the X than in all the rest 
combined. This, of course, is not because the X has more 
genes, but because its haploid condition in males and the 
unique character of its transmission make detection a great 
deal easier than for autosomal genes. Of the more than 
twenty available examples, the best known are red-green 
color blindness and hemophilia. Although hemophilia has 
been more widely publicized because of its notorious pres- 
ence in the former royal houses of Bourbon in Spain and 
Romanoff in Russia, 14 it affords a poor example, since no 
definite cases of affected women have ever been reported, 
probably because the female environment prevents its ap- 
pearance. The more typical behavior of color blindness will, 
therefore, serve us better (Figs. 46, 47). 

14 It was through the desperate efforts of the Czarina to find some form of 
relief for the chronic bleeding of her son, the Czarevitch, that Rasputin 
came into power. His evil influence was a factor of importance in the out- 
break of the Russian Revolution. Thus the gene for hemophilia has con- 
siderable historical importance! 



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"A color-blind male transmits his defect only to his grand- 
sons through his daughters, never to his sons, but a color- 
blind mother, even though her husband is of normal vision, 
always transmits her defect to all her sons. This is precisely 
the mode of transmission of the X chromosome in man, and 
a sex-determining X chromosome bearing the genes for these 
traits had to be assumed to explain this type of heredity even 
before it was discovered under the microscope." 15 

Drosophila has at least one gene located in its Y-chromo- 
some, and it is possible that a few of our genes, too, are lo- 
cated in this minuscule chromosome. This raises an interest- 
ing question. How would such genes be inherited? Would 
they form a completely independent, though small, linkage 
group limited to the male? Or do genes in the Y-chromosome 
have alleles in the X with which they can, at least occasion- 
ally, exchange places? For, though most of the genes of the 
X have no alleles in the Y, this is no assurance that the few 
genes of the Y might not have alleles in the X-chromosome. 
The situation was long assumed to be the former, and several 
examples of "sex-limited" inheritance were attributed to lo- 
cation of the responsible genes in the Y-chromosome. Sex- 
limited traits in vertebrates are, however, brought about by 
another means, and more careful investigation of the best- 
known case, the "bobbed-bristle" gene of the fruit fly, has 
shown that it, indeed, has an allele in the X, and that it 
crosses over with it occasionally. In fact, it is now clear that 
almost one half of the X-chromosome of Drosophila is, like 
the Y, practically empty of genes, and the allele of the 
bobbed-bristle gene lies in this portion. 16 The main gene- 
containing part is stuck on to this "empty" portion as an ap- 

15 Dunn, L. C. Heredity and Variation, p. 72. University Society, New 
York, 1934. This short book is by far the best treatment of the subject for the 
lay reader which has yet appeared. It succeeds eminently in being readable, 
in avoiding unnecessary technicalities, and in dealing with the major values 
of an understanding of genetics. 

16 The Y-chromosome of the fruit fly also carries two separate "factors" 
(whether or not they are comparable to other genes cannot be said) which are 
essential to the fertility of the male. 


pendage. The true relation between the X- and Y-chromo 
somes is that of a potent sex-determining fragment, carrying 
also many other genes, attached to one of a pair of singularly 
empty chromosomes (Fig. 48). This explains why the appar- 

Fig. 48. Diagram showing (in white) the portion of the X-chromosome of 
Drosophila that is homologous to the Y-chromosome. The normal Y is to 
the right. 

ently dissimilar X and Y act as a pair and regularly segregate 
in meiosis. Recently a new significance has been attached to 
the Y and various other parts of certain chromosomes which 
seem to be empty of genes. Although these parts of the 
chromosomes do not carry genes like the rest, nevertheless, 
their importance may be considerable. For we now know 
that the action of many genes, their dominance, or their 
mode of expression may be modified by their position with 
respect to such "inert" material within the same chromosome. 
This is by no means the whole story of the development 
and significance of sex, but its place in the hereditary pattern 
of an individual at life's outset is sufficiently clear without 
further discussion. The grand cycle of meiosis and syngamy 
redistributes the mutations of the ancestors in ever varying 
combinations, some good, some not so good, to their offspring; 
and through natural selection they are then weeded out. 
Thus is produced the fitness of life-forms for their environ- 
ment. Thus, too, through constantly arising mutations there 
enters each stock a flow of new variation through which is 
preserved that adaptability of life-forms so essential to sur- 
vival in a. changing world. All this is the matter of evolution, 


which would require another book to treat as fully as it 

Through the situation of the genes in organized bodies, 
the chromosomes, which form the basic units of meiosis and 
syngamy, there arises the inheritance of traits in groups, the 
phenomenon of linkage. And, through crossing over, the lim- 
itations set by linkage upon variety in hereditary pattern are 
overcome, the unit in the pattern becomes the individual 
gene instead of the chromosome, and the possibilities of re- 
combination soar into the infinite. 

Finally, there is the phenomenon of sex determination, with 
its secondary effects, such as sex-linked inheritance. Basic is the 
sexual bipotentiality of every cell and organism. Superim- 
posed upon this is genie control of the time of sex determi- 
nation, bringing as its by-product— significantly for us— the 
isolation of the sexes. Last comes sex determination for the 
diploid organism achieved potentially by segregation and 
realized at the moment of syngamy— the balance of sex genes 
inclining one way toward femaleness, the other toward male- 

How sex is realized is a part of the story of development, 
which we are now ready to survey. During development the 
various features of the environment may even, in the lower 
animals, play so profound a part that the predetermined sex 
is overruled and completely reversed. This is true not only 
of sex but also of every other element of the hereditary pat- 
tern. The expression of each gene or gene complex is utterly 
dependent upon the environment. Our hereditary pattern 
is in a sense only the accumulated hereditary control of our 
race over certain features of our environment. That control 
is far from complete or perfect. Development is the constant 
interplay of our genes and our environment; we ourselves 
are the arena in which the contest is played to its close. 


The Basis of Growth and Development 


IKE all life-processes, growth and development consist es- 
. Jsentially of controlled chemical and physical transfor- 
mations of matter. This is really but another way of stating 
our fundamental axiom that all the characteristics of an or- 
ganism are produced by the interaction of its heredity and its 
environment— that the two can never be divorced. For the 
controls of these processes are such that every organism re- 
sembles its parents, and in this lies heredity; while the chem- 
ical and physical transformations of matter can take place 
only where conditions are appropriate-and this is the action 
of the environment. 

Even the autocatalysis of the genes cannot occur except 
where raw materials and energy are supplied. The cyto- 
plasm of the cell represents their necessary environment. Nor 
can a human cell live successfully apart from the balanced 
environment of the body, with its checks and controls against 
sudden or extreme fluctuations of a chemical or physical char- 
acter-unless in a skillfully simulated duplication of it. As 
development proceeds, our cells acquire different forms and 
become suited to carry on different types of work, according 
to their situation and relations to the rest of the organism 
and the outer world, but also according to their own innate 
capacities. Life and environment are no more separable on 
this level of existence than on any higher plane. 1 

i See Sears, P. B. Life and Environment. Bureau of Publications, Teachers 
College, Columbia University, New York, 1939. 


A certain breed of rabbits lays up white fat on a diet of 
mash and potatoes, yellow fat on a diet of mash with green- 
stuffs. But most rabbits lay up white fat on either kind of 
diet. Considering only the first kind of rabbit, the variation 
in environment seems to be the decisive factor. But with both 
kinds of rabbits fed on green food it is the genetic constitu- 
tion that obviously makes the difference. We can appreciate 
the effects of heredity on the one hand, and environment on 
the other, only when we isolate one through neutralizing the 
effect of the other, that is, when we render it constant. Here- 
tofore we have discussed the effects of heredity while assum- 
ing that environment was constant. In Chapter V we shall do 
the opposite. For the present, we must try to relate the two 
to each other. 

Growth and development involve the absorption and as- 
similation of materials. This is mainly water, for the bulk of 
all protoplasm— two thirds of the body weight in man— con- 
sists of water. But the characteristic sizes, shapes, and types 
of organization assumed by developing organisms are obvi- 
ously not a simple matter of the imbibition of water or the 
absorption of other simple substances, such as salts, however 
essential these may be. Growth and development involve an 
increase in volume and a change in character of a colloidal 
protein system. It consists to a large extent of chemical syn- 
theses. The controlled chemical transformations of matter 
that underlie growth and development differ markedly from 
those involved in other primary metabolic processes, such as 
hydrolysis, oxidation, and fermentation. The latter are de- 
structive and energy-releasing, while the former are construc- 
tive and hence consume energy. 2 

The materials for these syntheses are the products of di- 
gestion, mainly those of protein digestion, the amino acids. 
It is true, of course, that both carbohydrates and fats are syn- 
thesized in our bodies, too; yet this is merely laying up a 

2 This contrast is what the biologist has in mind when he divides metabo- 
lism into catabolic and anabolic phases. 


reserve food supply, and consists principally of producing 
insoluble foodstuffs from soluble ones. Aside from water, the 
great mass of the living matter, the protoplasm itself, is 
mainly protein, along with various complex phospholipids 
and sterols. The syntheses of proteins are substantially simi- 
lar to those of fats and carbohydrates, for all represent a re- 
versal of the hydrolysis which splits larger molecules into 
smaller ones during digestion. The splitting action of water 
molecules (H-O-H) depends upon the addition of a hydro- 
gen atom to one portion of the molecule to be digested, and 
a hydroxyl (OH) group to the other, with a consequent sepa- 
ration at the connecting bond. Conversely, synthesis mainly 
involves dehydration. A hydrogen atom from one amino acid 
unit and a hydroxyl group from another are removed to 
make a molecule of water, and the units are bonded together 
at the points of loss. 

The distinguishing characteristic of an amino acid is the 
presence of both an amino group 


and an organic acid (carboxyl) group 


in the molecule. The dehydration synthesis of proteins from 
amino acids proceeds through a loss of a hydrogen atom from 
the amino group and a loss of a hydroxyl group from the acid 
group (these combine to make water), and a resultant bond- 
ing of the amino and acid groups of the two units. This we 
can diagram simply, if we let R stand for the bulk of each 
amino acid. The hydrogen atom and hydroxyl group that 
come out and the water they combine to make are each itali- 
cized for identification. Then: 




R H 


H O 

\y / 


1 II 
N G 

\ /\/. 

N G 

/ \ / \ -^ 

1 II 
H O 

R H H 

R H H O 
H C N G 

\ /\ / \ / \ 
N G G O 

+ HtO 

1 II A \ 

H O R H H 

The double group thus obtained still has an amino group 
on one end and an acid group on the other. This enables 
it, like any simple amino acid, to enter into further com- 
binations, until finally thousands and tens of thousands of 
such units may be combined into the huge protein group- 

Hydrolysis releases energy, but in very small amounts com- 
pared with those obtainable from oxidations or even from 
fermentations. The converse synthesis requires energy, but 
only to a corresponding degree. Growth is consequently a 
very economical process, one which consumes but little of 
our available energy. The limiting factor in the growth of 
malnourished and half-starved individuals is to be found in 
the lack of particular foodstuffs which are essential for cer- 
tain syntheses rather than in a generally inadequate supply 
of energy. This is a consideration of very great value in in- 
dicating the direction we should take in planning the satis- 
factory diet. 

Water, to be sure, will neither split large .molecules nor 
bond smaller ones into larger, unless the reaction is cata- 
lyzed. Whether we are digesting or, conversely, synthesizing 
new proteins, enzymes are required; and presumably the char- 
acteristic nature of human proteins, the product of the syn- 


theses, is due to the specificity of the enzymes controlling 
them. Let us, for example, imagine ourselves sitting down to 
a sizzling beefsteak. It is composed of proteins of specific 
kinds, recognizable as definite beef proteins. We eat our 
steak, digest it step by step into its component amino acids. 
It is then absorbed and carried by the blood to our cells. 
Here begins the task of synthesis. Proteins are to be recon- 
structed from these amino acids. Enzymes for the dehydra- 
tion syntheses are produced, and unit by unit the proteins 
are built up. When all is complete, however, the proteins 
are not beef proteins, but characteristic human proteins. 
Here are the same units, but combined in different propor- 
tions, in different arrangements! We might go so far as to 
say that we differ from the cow because we have different 


Different proteins in turn imply different synthetic pat- 
terns, controlled by different enzymes and precursors. Now 
why should human cells produce distinctively human groups 
of enzymes and beef cells distinctively beef groups of en- 
zymes? The distinction is clearly a hereditary one. Parents 
produce offspring of their own kind because mitosis ensures 
a lineal descent of genes. The action of the genes must con- 
stitute a control over the cytoplasmic production of enzymes 
and the simpler constituents which are the precursors of the 
ultimate products. 

Growth and development primarily involve specific chemi- 
cal syntheses, which depend on specific enzymes and precursors, 
which in turn depend on characteristic genes, which are inher- 
ited. We need, then, to learn how genes interact with one 
another, and how they control the production of secondary 
substances, if we are to arrive at an understanding of this 
aspect of life. Growth and development are secondarily mat- 
ters of differentiation within an individual, the appearance of 
distinctive form and structure through the specialization of 
cells, the emergence of a "division of labor." This chapter 


is, therefore, divided into two main sections, the first of which 
deals with gene and enzyme interactions. 


In Chapter II there was described a certain kind of gene 
interaction, that of alleles. These, we learned, may blend in 
their effects, or one allele may completely dominate the 
other, recessive allele. All too common, however, is the mis- 
conception which limits gene interaction to alleles. On the 
contrary, many, if not most, genes affect a variety of traits, 
and there need be little reserve in asserting that all traits are 
the product of the interaction of a number of genes. 

Most genes produce a number of effects 

We have taken the gene which is responsible for albinism 
as our example a number of times. It may serve again. In 
the first place, it is not limited in its effect to an absence of 
pigment in the superficial layers of the body. It has also a 
pronounced effect upon the disposition, at least in mice, rats, 
and rabbits. "White" rats, mice, and rabbits are far gentler 
than their pigmented relatives, even when sibs of the same 
litter. That is why they are generally preferred as pets. An 
albino rat is mild and curious. It can be held in the hand, 
and likes to explore sleeves and pockets. A normally pig- 
mented gray rat can hardly be handled so boldly. Only pa- 
tient training will curb its readiness to bite. 

This is a single example. There is also proof that the mul- 
tiple effect of genes is rather general. It comes from the study 
of deficiencies, of losses of pieces from a chromosome. Many 
of these losses are so small that they involve, in all likelihood, 
only a single gene. 3 Yet there are relatively few deficiencies 
which are not lethal when homozygous in the individual. 

3 In Drosophila, the extent of these deficiencies can be studied in the giant 
salivary gland chromosomes. Many represent losses of only a single cross- 
band (see Fig. 3), and the number of these corresponds closely to the total 
number of genes, as estimated in other ways. 


Most of them, in fact, are lethal even to single homozygous 
cells, though these cells may be surrounded by viable (hetero- 
zygous) tissues. These facts point to actions of the genes 
far more vital than any mere alteration of pigment or de- 
termination of hair or bristle form. Most genes are essential 
to the life-processes of each individual cell The effects we 
commonly observe are only superficial. 

Most traits involve the interaction 
of a number of genes 

The difference between our two common eye colors, brown 
and blue, is due to a single pair of alleles {B, b). The heter- 
ozygous combination, B/b, is a blend, variously known as 
gray or hazel, with the brown usually predominating over the 
blue. But eye color is not solely determined by this pair of 
genes. We have already learned that when the genotype of 
an individual is homozygous for the "albino" gene (a), there 
is no pigment in the iris of the eye, and the red of the hemo- 
globin in the blood makes it appear pink. In an albino the 
genotype must include the other pair of genes, too, for all 
pairs are normally represented, but here this second pair fails 
to produce any effect. If, however, the genotype, as respects 
the albino gene, is A/ A or A /a, then the eye color is fixed 
by the genotype of the second pair, B/B, B/b, or b/b. Why 

is this? 

If we consider the chain of chemical syntheses leading up 
to the final production of pigment in the eye, it will become 
clear that the genes which control earlier steps in the chain 
will exert such influence that they may alter or nullify the 
action of genes controlling later steps. They possess a marked 
precedence (epistasis) over them. In fact, just as we may shape 
and bake a lump of dough in various ways, but without 
dough can bake no bread, so here the genes producing brown 
or blue color in the iris only alter a substance already pro- 
vided, and in its absence can do nothing. Figure 49 is a sim- 
ple diagram to illustrate the situation. 


This by no means completely describes the situation. The 
hazel phenotype is extremely variable (gray, green, violet, 
apparent brown), and this in turn rests upon the action of 
still other gene pairs, so-called "modifiers." 4 

A/A 3/3 


*/ a <=^ b/b- 



Fig. 49. The heavy arrows represent alternatives in the chain of chemical 
reactions concerned in the production of eye pigment. Alternative genotypes 
are placed above one another at a specific point in the chain-reaction, and 
the small arrows indicate respectively the direction taken by the chain- 
reaction for each genotype. 

Another possibility is that two or more pairs of genes may 
affect the same stage in the chain of reactions leading to the 
expression of a trait. An example lies close at hand. We can 
find it in another end-reaction of this same chain, that which 
produces pigment in the skin. The early part of the chain is 
the same. (As a matter of fact, one frequent sign that a gene 
pair precedes others in its action is the wider extent of its 
effect within the organism. Thus the nonalbino-albino pair of 
genes is body-wide in its effect, while the later-acting genes 

4 A mating between individuals, each heterozygous for both of these pairs 
of genes (A/a;B/b), will result in a modification of the typical 9:3:3:1 
phenotypic ratio expected from a dihybrid cross. It will, assume the form 
9:3:4, since the entire one fourth of the progeny having the genotype 
a/a will be albino, regardless of the genotype of the other pair. Whenever 
the dominant of a primary pair, rather than the recessive, inhibits the ex- 
pression of the secondary pair (we may visualize this by switching the posi- 
tions of a/a and < ' in Fig. 49), then the ratio becomes 12 : 3 : 1. Such, 

in dogs, is the interaction of a primary pair (no pigment in hair versus pig- 
ment) with a secondary pair (black versus brown), which gives an F 2 ratio 
of 12 white : 3 black : 1 brown. Moreover, a pair itself like the nonalbino- 
albino pair may be subject to the precedence of a dominant inhibitor. In 
poultry the lack of color in White Leghorns is due to the latter, while in 
the White Silkie breed it is due to a recessive. In the F 2 from a cross between 
them, 13 white : 3 colored are obtained. Precedence may thus produce quite 
a variety of results. 


are limited in expression to a portion of the organism, such 
as the eye, or the skin.) The final reaction appears to be 
catalyzed by two pairs of genes, the alleles in each of which 
blend, while each pair is exactly comparable in effect to the 
other. We may denote the genes producing heavy deposits 
of melanin as S and T, and their respective alleles, which 
produce only slight deposits, as s and t; and then diagram as 
before (Fig. 50): 









Fig. 50. The chain-reaction leading to the production of skin pigment. 
See Fig. 49. 

As a consequence of the type of interaction we find here, 
it follows that a mating of black and white will always pro- 
duce mulattoes, a very uniform class; for: 








A mating between mulattoes of this genotype results in a 
way surprising to most of us, in fact, quite confounding 
many of our preconceived opinions, as the following diagram 



X S/s;T/t parents 



s;tj gametes 






S'T C 


S'T C 

s t 



S'F C 

S l ™ 

s ; r M 

s T iwr 

s ; r M 

S ; t Br 



~i'T C 

S l mr 
-; T M 


s T 

s ; T Br 


S T n/r 

St Br 

l't Br 

- S ;?Br 

S t 


Black (B) —1 

Chocolate (C) — 4 

Mulatto (M)— 6 

Brunette (Br) — 4 

White (W)— 1 

Mulattoes may have completely black or completely white 
children! In fact, the expectation for either of these is quite 
high, 1 in 16. 5 Moreover, these extreme types are both ho- 
mozygous, and, therefore, not only appear pure black and 
pure white, but will breed as pure black or pure white, re- 
spectively. What a far cry this is from the common belief 
that racial intermixture permanently contaminates the her- 
itage of every descendant! With this example we begin to 
see what Mendel's first principle really signifies. Because 
heredity is due to units, genes, which segregate and re- 
combine generation after generation without themselves be- 
ing affected, it must follow that segregants such as these pure 
whites and pure blacks will emerge from hybrid matings. 

5 This is according to Davenport, who has studied the matter most thor- 
oughly. Some other geneticists are inclined to think that more than two 
pairs of cumulative factors are concerned in skin pigment and hence that 
the expectation for pure black or pure white children of mulattoes is not 
more than 1 in 64. On the other hand, matings of whites with half-caste 
Bantu negroids in South Africa frequently produce children with white 
skins, blue eyes, and straight yellow hair. The difference in skin color may 
here depend upon only a single pair of genes. 


L 73 

These segregants, insofar as these two particular pairs of 
genes are concerned, inherit from only two of their four 

In our own country, a large part of the racial intermixture 
going on comes from matings of white with brunette or 
mulatto types. This, in contrast to mulatto by mulatto mat- 
ings, results in a greater proportion of white segregants and 
an increase in the brunettes, who are frequently light enough 
to pass as white, and often do. 

(a) S/s;T/t X s/s;t/t (b) S/s;t/t X s/s;t/t 





i S/s;T/t mulatto ( 

i S/s;t/t + s/s;T/t brunette { offspring 

| s/s;t/t white [ j i s/s;t/t white 

The gradual infusion of white "blood" into our American 
Negro stock is, of course, recognized by everyone, but not 
everyone has been equally ready to see the impracticability 
of treating the pure white segregants of hybridization as 
blacks. A more poignant expression of the problem is to be 
found in the personal difficulties of the pure white segregants 
who are reared in mulatto families. 6 

It is, of course, true that there are other negroid traits 
besides blackness of skin, yet these are few in number. 
There is a dominant gene for kinky hair, and a pair or two 
for facial features. In all, it is unlikely that there are many 
more than six pairs of genes in which the white race differs 
characteristically, in the lay sense, from the black. Whites 
or blacks, however, unquestionably often differ among them- 
selves by a larger number than this, a fact which reveals our 

6 These were excellently portrayed in the movie, "Imitation of Life," which 
appeared in 1935. 



racial prejudices as biologically absurd. It is only the con- 
sistency of the difference, not its magnitude, which looms so 
large in our eyes. Differences between other races are prob- 
ably even less, and those between such sub-racial groups as 
"Nordics" and "Mediterraneans" are negligible. The chasm 
between human races and peoples, where it exists, is psycho- 
logical and sociological; it is not genetic! 

The interaction of gene pairs in the manner just illus- 
trated by those for skin color may be called cumulative, 
since the alleles of the two pairs are equivalent in effect and 
additive in action. A slightly different cumulative result ob- 
tains whenever the alleles in each pair are dominant and reces- 
sive. In Duroc-Jersey hogs, for example, the typical red color 
results from an additive effect of two dominants, each be- 
longing to a different pair, and either alone producing a 
sandy color, while the double recessive is white. By referring 
to the checkerboard diagram (p. 172), we can figure out that 
there would be an F 2 ratio of 9 red : 6 sandy : 1 white. 

Somewhat more frequent are instances in which the dom- 
inants produce an equivalent, but not an additive, effect. 
Thus they are duplicates of one another, and only 1/16 of 
the F 2 progeny will express the recessive trait; that is, the 
expected ratio is 15 : 1 . Feathered shanks in poultry and the 
typical triangular, rather than ovoid, seed capsules of the 
world's most widely distributed weed, shepherd's purse 
(Bursa), are inherited as just such duplicate dominants. 

Finally, there are instances in which either dominant 
alone is ineffective, and the trait is produced only by their 
interaction. Normal hearing in man appears to be of this 
class, judging from a number of pedigrees; while the con- 
trasting trait, deaf-mutism, is the consequence of the absence of 
either dominant allele (D or E). Two deaf-mute parents may 
thus have all deaf-mute children, or no deaf-mute children, 
depending upon whether their own deafness is due to the .ab- 
sence of the same dominant, or of different dominants, respec- 
tively (1) D/D;e/e X D/D;e/e and (2) D/D;e/e X d/d;E/E. 


This could not be the case were deaf-mutism due to either a 
dominant or a recessive single gene. Many other examples 
of this type are known, especially among plants. The 9 : 7 
ratio 7 which is produced in the F 2 by such a "complemen- 
tary" interaction was first discovered in the flower color of 
the sweet pea, in the early days of genetics (1900-1910). The 
characteristic purple color of the petals comes from a pig- 
ment (an anthocyanin) which is synthesized from two com- 
ponents. Each of the dominant alleles of the two pairs of 
genes concerned is essential for the production of a particular 
one of these components. 8 

Quantitative variation, insofar as it is genetic, 
depends upon the cumulative action 
of multiple factors 

A moment's reflection, and we can see that the traits we 
have hitherto used as examples are qualitative; they are not 
continuous variations, like height or weight, along a quanti- 
tative scale. Yet we worry principally over the latter sort 
when we wonder about our normality. Are we too tall or 
too short? Are we too fat or too thin; overweight or under- 
weight; healthy or sickly; intelligent or stupid? These char- 
acteristics are extreme variants in continuous distributions 
which have an average. Are we sufficiently near this average 
to be normal? Perhaps all of us have at some time doubted. 

A rude indication of continuous quantitative variation is, 
nevertheless, already apparent in the example which showed 
how two pairs of genes act cumulatively to determine skin pig- 
mentation; indeed, we may even discern it in simple blend- 

7 That is, 9/16 of the offspring will carry both dominants; 3/16 will carry 
the first dominant but not the second; another 3/16 will be just the reverse; 
and 1/16 will carry no dominants. The sum of the classes with only one 
dominant or with none is 7/16. (See checkerboard diagram, p. 172.) 

8 The "throwbacks" and "reversions" of the breeders may be due merely 
to the homozygous reappearance of a recessive trait. On the other hand, 
they are probably more often examples of the reunion in one individual 
of complementary factors long isolated in different stocks. 



ing, as in the pink four o'clocks, for example. For, if we dia- 
gram the relative frequencies of the various classes, we obtain 
a figure highest in the middle and falling off symmetrically 
on either side— that is, with the most abundant class the in- 
termediate one (Figs. 51, 52). 

Fig. 51. Block diagram and frequency curve to illustrate the quantitative 
distribution of phenotypes in the F 2 generation from the cross of red by 
white four o'clocks. 

In Figs. 51 and 52 the area above each unit along the base 
line represents the relative frequency of the respective class. 
These block-shaped figures may also be expressed in the form 
of curves superimposed by connecting the midpoints of ad- 
joining classes, and this makes it easier to compare the dis- 
tributions at a glance. 

Fig. 52. Block diagram and frequency curve to illustrate the frequency of 
the various phenotypes among the offspring of mulattoes. 

Were we to plot the results in the F 2 generation from a hy- 
brid mating involving three pairs interacting in this same 
cumulative fashion, we would get phenotypic classes in the 
ratio 1 : 6 : 15 : 20 : 15 : 6 : 1. A mathematician would 
quickly see that each of these three ratios is an expansion of 
the expression (a + b) n , where n is, respectively, 2, 4, and 6. 


(This is known as the Binomial Expression, and its expan- 
sion to any power forms a binomial distribution.) Once we 
realize that these ratios are all expansions of the same simple 
expression to various powers, we can calculate the binomial 
distribution— in other words, the phenotypic ratio— for any 
number of pairs of interacting genes. If we do this, we find 
that as n increases— as more and more pairs of genes are con- 
cerned—our distribution approximates ever more closely the 
bell-shaped curve in Fig. 53. This curve, therefore, expresses 

Fig. 53. The normal frequency curve derived from the expansion of 
(a -f- fr) 2 o, corresponding to the frequency distribution of a characteristic 
determined by twenty pairs of interacting genes. 

the normal probability of inheriting any degree of a quan- 
titative trait determined by a great many genes. 

The normal frequency curve expresses graphically and 
concisely what is really meant by "being normal." Only a 
frequency distribution itself can truly be normal. Wherever 
we set limits, on either side of the distribution's mean, 9 lim- 
its within which lie the "normal" and beyond which the "ab- 
normal" commences, we are necessarily arbitrary. For, 
whether the variation in the distribution is due to the ran- 

9 The mean is the commonly used arithmetical "average." It is found by 
adding the scores (or measures) of the individuals in a distribution, and 
dividing by their number. If the individuals are grouped into classes, the 
mean becomes 2/F/n, where 2 stands for summation, / is a class frequency 
and V its value, n being the total number of individuals. 


dom segregation and recombination o£ many pairs of genes, 
or to chance environmental factors, or, as is most likely, to 
both, in any case the extreme deviations from the average 
are normally to be expected in their due proportions. It is 
no more just to speak of an extremely tall or extremely 
stupid person as abnormal than it is to think of brown skin 
as normal and black skin or white skin as abnormal. The 
latter are simply extremes in a rather discontinuous distribu- 
tion, while tallness and shortness, moronity and genius, are 
extremes in continuous ones. 

Nevertheless, there are individuals who appear to lie en- 
tirely outside the continuous normal distribution— a person 
nine feet tall or one weighing 450 pounds. There are groups, 
too, which seem to form secondary normal frequency distri- 
butions alongside the major one, so that a bimodal 10 curve 
is produced. There are, for instance, the midgets in the 
height distribution and the imbeciles, idiots, and feeble- 
minded in that for intelligence. Here we meet a discontinuity 
which is due to the effect of some preponderant factor, ge- 
netic or environmental, acting differentially in the major and 
secondary groups. When two such distributions overlap, it 
becomes impossible to say offhand to which one any par- 
ticular individual from the overlapping region belongs. Is 
Jeff a tall midget or merely a short man? Only a careful 
study of his family pedigree, childhood diet, and health 
record may enlighten us as to which of two normal distribu- 
tions, the midget or the "normal," he belongs. 

Whenever the differential factor acts infrequently, the rare 
affected individuals either stand alone or are unrecognizably 
merged with the extremes of the normal distribution. Here 
we cannot help but be arbitrary. Yet we can at least set the 
limits of the normal distribution so that there is but a negli- 
gible chance that anyone falling outside them is actually an 

10 The mode of a distribution is simply the point (or class) of highest 
frequency. When a distribution has two such "peaks," separated by a 
"valley," it is said to be bimodal. 


extreme variant of the major group. Even the most extreme 
5 per cent of the distribution is not a negligible portion, for, 
with respect to each quantitative trait, one individual in 
every twenty would on this basis be classed as "abnormal." 
Scientists, with customary caution, usually set the thresholds 
of significant, that is, of non-random, deviation from the aver- 
age where only 0.13 per cent of the distribution lies beyond 
them at each extreme. 11 This means that only one individual 
in 400 will be erroneously regarded as "abnormal" when he 
is really only an extreme variant of the random variation 
characteristic of the group. 

When individuals of the second generation from any cross 
between extremes which differ because of "multiple factors" 
are bred together, there is a slight but definite probability that 
any single one of the offspring will be as extreme as either par- 
ent. There is an overwhelmingly greater likelihood that an 
individual will be intermediate— "average." Now within 
large mixed populations such as ours, most individuals will 
be heterozygous for the majority of whatever multiple factors 
are involved. That is, most of us are like the first-generation 
offspring of extremes. For this reason we can expect the chil- 
dren of average couples among us to correspond to the prob- 
abilities of the curve for all such traits as height, weight, men- 
tality, general vigor, and resistance to disease, insofar as these 
are inherited. 

11 This proportion of the area of the normal curve is determined from 
the standard way of measuring the variability of a normal distribution, by 
calculating the standard deviation (a). This is the square root of the sum 
(2) of the squares of all (/) deviations (d) from the mean, divided by the 

number of individuals (n) in the distribution (a = \f ). The standard 

deviation, when laid off on both sides of the mean, includes 68.26 per cent 
of the area of the normal curve, and ^ 30" includes 99.74 per cent of the 
area; that is, all but 0.26 per cent. Here we have one of the most valuable 
of all statistical measures to the scientist, who is constantly wanting to know 
whether a certain difference he observes is probably due to chance or has 
other significance. To be sure, the choice of ^ 30* as the criterion of signifi- 
cance is arbitrary— but it is conservative and consistent. The trouble with 
most of our judgments as to the significance of differences we see is just 
that they lack these two qualities. 


In the development of all such general characteristics as 
these, environment too plays a large part. Its influence may 
even preponderate in many instances. For example, while the 
variability in height within the Japanese nation and within 
our own is probably by and large genetic, recent observations 
show that at least a very considerable part of the average dif- 
ference in stature between Japanese and Americans is a re- 
sult of the relatively deficient Japanese diet. This is sub- 
stantiated by the fact that our own people have been gaining 
in stature, generation by generation, and children of immi- 
grants, especially, tend to be taller than their parents. The 
whole question of the relative importance of heredity and 
environment is so vast and significant for our thinking that 
we shall return to it for fuller consideration at the end of 
this chapter. Meanwhile let us see what is understood about 
the way in which the genes control the production of traits, 
that is, how they regulate the characteristics of the internal 


The cytoplasm forms the environment of the genes. From 
it they must receive needed substances; to its conditions they 
are adapted; and whatever effects this community of repro- 
ducing proteins can bring about in the organism must be 
achieved by their modification of their immediate environ- 
ment. In this respect the society of the genes strictly resem- 
bles our own. 

Perhaps these considerations border on the obvious. Yet 
it is just here that our ignorance is most abysmal. Biochem- 
istry has made enormous strides in the past century, yet we 
know little about the intricate series of reactions leading to 
the final production of even a single trait. 

It is certain, however, that many genes are limited in their 
effects to the cell in which they lie. There are two ways of 
testing this. One is to study the effects of nondisjunction or 


crossing over in body cells. Either of these rather infrequent 
events may render a cell homozygous for a recessive gene 
for which the rest of the body is heterozygous. 12 We might 
expect this cell and its descendants to be no different from 
the neighboring cells if its traits depend upon diffusible or 
circulating substances. If, on the other hand, the gene prod- 
ucts 13 are confined to the cell in which they are manu- 
factured, the homozygous group of cells would differ from 
the surrounding heterozygous cells and form a distinctive 
spot. In the fruit fly a large number of genes have been 
tested in this way, and of them all only two or three appear 
to involve the production of diffusible substances. In plants, 
too, variegation in flowers, leaves, or seeds is very frequent. 
While hormones are, no doubt, much more important in 
vertebrate development than in that of insects, there is some 
evidence of mosaicism even among the vertebrates. Many of us 
have seen people with differently pigmented sectors of the iris 
or with eyes of different color. A few years ago the illustrated 
papers featured a child whose head showed a sharp division 
exactly down the middle, with brunette complexion, dark 
hair, and brown eye on one side, and blond complexion, 
sandy hair, and a blue eye on the other. This lad in a way 
resembles the insect gynandromorphs, which result most 
commonly from the loss of a sex chromosome in one of the 
first two cells formed during development. These oddities 
are male on one side and female on the other, and sex-linked 
recessive traits show up on the male side. 

The other experimental method of testing the autonomy 
of genes within their own cells is through the technique of 
transplantation. Genetic research in America was still young 
when experimenters at Harvard University (W. E. Castle 

12 For an account of the way in which this is brought about, see A. H. 
Sturtevant and G. W. Beadle, An Introduction to Genetics, pp. 344-347 
(W. B. Saunders, Philadelphia, 1939). This textbook is most highly recom- 

13 This can be taken to mean either substances directly produced by the 
gene, or those produced in the cytoplasm as an indirect result of the gene's 
abstraction of substances from it and its consequent alteration. 


and J. C. Phillips) tried removing the ovaries of an albino 
guinea pig and implanting those from a black female in their 
stead. The operation succeeded, the female was mated to 
an albino male and had six young— all black! This showed 
that the dominant genes for black coat present in the im- 
planted ovaries had not been altered. No doubt this was to 
be expected, since the genes in the implanted ovaries and, 
subsequently, in the "black" embryos were not exposed to 
any more radical influences than are usual for embryos. And 
embryos, although exposed to the maternal environment, in 
most cases develop according to their own genotypes, not 
their mother's. 

Rudiments of the adult eye may be transplanted from a 
fly larva into the abdominal cavity of another larva. They 
will then develop into complete eyes, pigment and all, ex- 
cept that they will be inside out. This technique provides a 
means of testing whether the genes for eye characters are 
autonomous, simply by introducing eyebuds of one geno- 
type into hosts of a different genotype. The results fully 
confirm those obtained by the other method. Of all the 
numerous eye characters tested, only two ever showed any 
influence of the host upon the implant. 

Superficial transplantations from one species of salamander 
to another have also been tried. Here it was found that trans- 
planted cells retain such characteristics of their origin as 
pigmentation and cell size, even though they may migrate 
considerably. On the other hand, they may enter into the 
formation of various parts of the host, according to their 
position. This is different from the rudiments of an insect's 
organs, which when transplanted have their fate already pre- 

These instances of the limitation of a gene's action to a 
single cell suggest that the genie products are held in by the 
cell membrane. If the nuclear membrane is like the cell 
membrane in its permeability toward these substances, per- 
haps its dissolution at the time of mitosis is the means of 


releasing the dammed-up genie products. This would ex- 
plain why development and cell division ever accompany 
each other, and why, as the rate of cell division slows down, 
the course of specialization also draws to a close. 

The extent of our knowledge and ignorance in this field 
will show up most clearly if we examine the best analyzed 
case, that of flower pigments. Some flower pigments (yel- 
low and orange) are insoluble and located in plastids. 
Others, the anthoxanthins (yellow, ivory) and the antho- 
cyanins (red, purple, and blue), are dissolved in the cell 
sap. Color variation may be due to the concentration 
of these pigments, but other changes are also important. The 
anthocyanins are hydrogen ion indicators, and vary from red 
at the acid end of the scale to blue at the alkaline. Some pig- 
ments, such as the ivory one, combine loosely with anthocy- 
anins and produce a disproportionate bluing effect; these 
are the co-pigments. Finally, additional hydroxyl groups or 
sugar residues or a loss of methyl groups or organic acid resi- 
dues, all make the anthocyanins bluer. Thirty-five genes 
from fourteen species or genera of plants have been studied, 
and in every instance the biochemical action of each indi- 
vidual gene is a simple affair. Thus the scarlet pigment pelar- 
gonidin may be rendered bluer by a dominant gene which 
adds an OH group at position 3 > '. Another dominant gene is 
then capable of adding another OH group at position 5', 


OC 6 H n O 

making the flower color still bluer, while a third dominant 
gene is capable of adding on both groups at once. Still 
further cumulative blueness may be obtained by a dominant 
gene which adds a sugar residue at position 5 and by an- 
other which is responsible for the production of the ivory co- 


pigment. There are also dominant genes acting in the reverse 
direction; in other words, there are both dominant and reces- 
sive genes for blueness. For instance, a single dominant gene 
may methylate the OH group at position 3' (changing it to 
— O.CH3). Another methylates both the OH groups at 3' and 
y. A third adds an organic acid residue at some as yet un- 
known position. A fourth renders more acid the pH of the 
cell sap in the flower petals, and in them alone. All these 
factors make the pigment redder. Without multiplying ex- 
amples, we can see that the dominant genes which bring 
about a specific change in the pigment molecule all add some- 
thing to it. Their recessive alleles are inactive. 

The anthocyanins and anthoxanthins are extremely simi- 
lar in constitution and are apparently produced only at one 
another's expense. This implies that they must compete for 
some common precursor, which is probably the ring marked 
A in the formula. There is a gene in the snapdragon (An- 
tirrhinum) which is essential for the production of both 
anthocyanin and anthoxanthin pigments and so must relate 
to the common precursor. The genetic changes in the other 
part of the molecule are probably accomplished before the 
final synthesis of the molecule. 

This situation may appear at first glance extremely com- 
plex, yet it is far simpler than we might have expected. The 
simple biochemical action of any one of these genes leads us 
to hope that it is not altogether beyond the scope of our 
analysis. Perhaps there is here only a single chemical step, or 
very few, between gene and known biochemical effect. Analy- 
ses of the dosage effects of genes tend toward the same con- 
clusion. Vitamin A in maize endosperm is produced from 
a yellow carotinoid pigment. A dominant gene (Y) is a factor 
for producing this pigment. Since endosperm is triploid, the 
effect of the Y-gene can be compared in dosages of o, 1, 2, 
and 3 units. The vitamin A content of the grains is approxi- 
mately proportional to these gene dosages. The gene can 
hardly be acting as an enzyme here, for enzyme concentration 


is rarely related directly to the amount of the product. The 
immediate product of the gene may be some component or 
precursor of the yellow pigment. Recessive genes, too, are 
frequently found to approach the action of their dominant 
allele as their dosage is increased. They appear to be "doing 
the same thing-but less efficiently." 14 The extreme of in- 
activity is represented by deficiencies. These are usually 
lethal; but when they are not, they may, like the deficiency 
for yellow body color in Drosophila, resemble the recessive 
alleles in effect. 

Yet we must beware of oversimplifying the problem. We 
must remember that even genes concerned with but super- 
ficial traits, judging from mere inspection, have proved to be 
vital to the cytoplasmic system. Where each gene may be con- 
cerned with a number of traits, even determination of its 
particular time and mode of action upon a certain biochemi- 
cal system very likely only opens up a lifetime of research to 
be pursued ere the gulf between gene and phenotype can be 
finally bridged by our chemical equations. 

At present, about all we can say is that most genes probably 
affect developmental reactions through control over either 
their rates or their durations. A classical example is the process 
of pigmentation of the eye of the crustacean Gammarus che- 
vreuxi. The black-eyed form is dominant; scarlet is recessive. 
During development the eye first appears scarlet. Then, in 
the presence of the dominant JS-gene, it gradually darkens, 
becoming first brown, then chocolate, and finally black. 
When the genotype is homozygous for the recessive (b) allele, 
the process is the same, except that darkening starts later 
and proceeds much more slowly, consequently being brought 
to an end at an earlier point in the process. Very likely the 
pigmentation of our eyes and skin is determined in a simi- 
lar manner. 

Now chemical reactions in general are susceptible to con- 

14 Sturtevant, A. H. and Beadle, G. W. An Introduction to Genetics, p. 337. 
W. B. Saunders, Philadelphia, 1939. 


trol in rate (a) by physical factors such as temperature, light, 
or the degree of dispersion of the substances; (b) by chemical 
factors such as pH, or variations in the concentrations of the 
reagents; and (c) by catalysts. In the case of flower pigmen- 
tation, we have already seen how a gene which controls the 
pH in a localized region of a plant, the flower petals, may 
control the end-result of a developmental process. However, 
since physical factors generally either are beyond the control 
of the organism or are kept rigorously constant, it is, no 
doubt, through the other two avenues that most rate-genes 
operate. The Y-gene in maize may be taken as an example 
of those genes which control rates by varying the available 
amounts of precursors. Genes which control growth by con- 
trolling the production of glutathione (see Chapter I) exem- 
plify control of a trait by means of enzymes. Inasmuch as the 
enzyme may not be an immediate product of the gene, obvi- 
ously both types of control may be involved in any single 
chain of processes. 

Control over the duration of a process upon analysis turns 
out to be a matter of rates, too. This is because the onset 
and cessation of a process likewise depend upon physical 
factors, reagent concentrations, and enzymes. Especially im- 
portant in this connection are two phenomena, threshold and 
maximum response. 

There is quite generally a minimum concentration which 
the substances determining a reaction must reach before they 
can act— this is the threshold. Together with the fact that, 
from individual to individual within the same genotypic class, 
there is normal variation due to "chance," the existence of 
thresholds is responsible for a considerable part of the con- 
fusion and difficulty in our thinking, past and present, about 
heredity. For when the effect of a particular genotype lies 
close to the threshold, normal variation will cause some in- 
dividuals to fall above it and others below it. In other words, 
individuals of the same genotype may differ in phenotype. 
Human heredity abounds in such instances, especially among 


hereditary diseases due to dominant genes. Such incomplete 
dominants, sometimes producing the disease and sometimes 
not, include hemolytic jaundice, a non-sex-linked type of 
hemophilia, polydactyly, and many others. It is, however, 
often difficult to determine, without recourse to experimental 
breeding, whether a trait is due to an incomplete dominant 
or to the interaction of two or more genes. 

Above a certain point, either at the threshold or higher, any 
further increase in gene potency or dosage is without result. 
This is the principle of maximum response. It also has a 
relationship to the dominance of genes. For a gene to be 
completely dominant, it must produce the determining sub- 
stance in such excess that no fluctuation of the environment 
will reduce it in amount below the threshold. Yet all alleles 
which exceed this limit will produce the same phenotype 
(in a common environment), since the concentration of the 
gene product is no longer a limiting factor in the processes 
of development. 

Between threshold and level of maximum response there 
may lie a region in which increasing gene potency or dosage 
results in greater amounts of the gene product, and this is 
correlated with increasing manifestation of the trait. Figure 
54 (p. 188) shows how these concepts may be applied to the 
white eye-color series of alleles in Drosophila, a typical se- 
ries with the highest alleles dominant and the lower ones 

Both modifying genes and environmental factors can alter 
phenotype and dominance. This they may do by changing 
the time at which production of the determining substance is 
begun or ended, or when its effective production is ended; by 
changing the level of maximum response or the threshold; 
or by directly affecting the rate of production of the gene 
product relative to the rest of development. 

Whether or not all genes act in this fashion, through con- 
trol over rates of reaction in a quantitative way, is at present 
highly controversial. Perhaps completely different or "quali- 



Fig. 54. A diagram to illustrate the relation of genie action in a series of 
alleles to thresholds and levels of maximum response. The effect produced 
by any genotype is indicated by the height at which the line representing its 
rate of production crosses the vertical line marked "Time A," at which the 
process under a given set of conditions is cut short. If the production line 
fails to reach the threshold by the time limit, no effect is produced. Any 
production line reaching the level of maximum response before reaching the 
time limit would produce the maximum response. Between the two levels, 
effect is roughly proportional to height above the threshold. The normal 
variation of each genotype is shown by the thickened bars where the pro- 
duction lines cross the time line. Should the normal variation of a genotype 
overlap either the level of maximum response or the threshold (see w e w), 
some individuals of that genotype would resemble the complete dominant or 
the extreme mutant, respectively. w + , normal allele of the white eye-color 
series (D. melanogaster); w e , eosin; w, white. 

tative" changes are also fairly frequent. But since we know 
nothing whatever of the mode of action of such changes, let 
us pass on to less speculative matters. 

Here one might well raise the question whether we are 
really justified in assuming that all heredity is genie, and 
that the cytoplasm plays only the part of a substrate in which 
the effects of the genes are worked out. There is certainly 
still room for controversy. However, except for a few cases 
where certain plastid characters in plants are directly trans- 
mitted, there is no indisputable evidence of any specific 
hereditary character transmitted through the cytoplasm. Nor 
are the majority of plastid characteristics directly inherited; 
most of them, on the contrary, are clearly determined by 

Nearly all instances of "maternal inheritance," which might 
be supposed to depend on cytoplasmic heredity, since only 


the mother transmits cytoplasm to the offspring, have now 
been found to be simply cases of delayed genotypic action. 
Thus the color of a silkworm moth's eggs is determined by 
her genotype rather than by that of the fertilized egg itself. 
In the mealmoth Ephestia the color pattern of the larva is 
determined by the maternal genotype through the first two 
molts. Then the larval genotype, with its paternal contribu- 
tion, becomes effective, and thus may produce a striking 


Often in crosses between different species or genera there 
is an effect of the maternally derived cytoplasm upon certain 
gene-determined traits; that is, reciprocal hybrids may con- 
sistently differ somewhat in phenotype, even though identi- 
cal, as far as we can tell, in genotype. Their offspring, in 
turn, show the same tendency to resemble their mothers in 
these respects. These observations simply mean that genes 
tend to act differently in different cytoplasmic substrates. 
There is also evidence that they work better in that of their 
own species than in another, while in very foreign substrates 
they cannot operate successfully at all. This does not mean 
that the cytoplasm has hereditary qualities like those of the 
genes. It is simply another indication of the interdependence 
of the genes and their immediate environment, which have 
become attuned to one another through eons of evolutionary 

On the outside, the cytoplasm is exposed to the condi- 
tions of the external environment and so is subjected to modi- 
fication. Some of these changes are transitory; others may 
be quite enduring. The effects of exposure to extreme tem- 
peratures or to chronic alcoholic poisoning upon the cytoplasm 
of germ cells-or of vegetative tissues that give rise to off- 
spring asexually-may be handed down for generations before 
they finally disappear. Even the general adaptation to par- 
ticular conditions of life-climate or diet, for example-may 
be of this sort, a pseudoheredity that would be readily mis- 
taken for the work of the genes themselves, were it not 


strictly maternal or somatic in transmission and far less en- 

The genes are thus buffered from the outer environment 
by their own surrounding cytoplasm. In many-celled organ- 
isms, each cell in its turn lives in the midst of a multitude 
of its fellows, constituting a larger living environment inter- 
posed between cell and outer world. This must also be 


At no time in our development after the first cell division 
or two, are we simply an agglomeration of cells. Always we 
are something more than the mere sum of heart plus brain 
plus digestive tract plus other organs. For at the outset 
the whole organism, as yet relatively simple in organization, 
performs all essential functions in a general way— as a whole. 
As development proceeds, parts of these general functions 
are delegated to each specialized structure. Yet no matter 
how autonomous they become, they can operate only if other 
parts of the body carry on the remainder of the general func- 
tions for them. Hence, the more specialized are the parts, 
the more integrated is the whole. 

If this seems abstruse, perhaps it may be more readily 
understood from an analogy with the molecule. A molecule 
of cane sugar (sucrose) is more than the mere sum of twelve 
carbon atoms, twenty-two hydrogen atoms, and eleven oxygen 
atoms. These must also be arranged in a particular pattern, 
for the same atoms, in various other relationships to one 
another, may form maltose, lactose, or any other disaccha- 
ride. Our present problem, then, is that of bodily pattern. 
How is the abstract pattern of the genes, a haphazardly 
arranged collection of potentialities, related to the visible, 
functionally arranged and integrated pattern of the body 
produced by development? 


The primary foundation of form lies in the fixation of the 
axes which determine the symmetry of the body. The first of 
these is already predetermined in the egg through the differ- 
entiation of animal and vegetal poles. In many species, as 
yolk is stored in the egg during its growth in the ovary, it 
tends to gravitate to the vegetal pole, while cytoplasm and 
nucleus occupy the animal pole. Many biologists have tried 
to find the reason for this first visible indication of the egg's 
polarity. Most of them have come to the conclusion that 
some factor external to the egg is responsible. Perhaps the 
position of the egg in the ovary allows one end readier access 
to oxygen than the other. At any rate, a gradient of metabo- 
lic activity is set up in the egg, and this would appear to be 
true even of such eggs as have evenly distributed yolk, like 
those of mammals. This metabolic gradient seems to fix the 
initial axis of the egg, and our anterior (head) and posterior 
(hind) ends come, respectively, from the animal and vegetal 

Every cell produces electricity as one of its characteristic 
forms of energy. Since cells formed at the animal pole are 
more energetic than the inert, yolk-filled ones at the vegetal 
pole, that end of the embryo is positively charged with elec- 
tricity. In at least some organisms, it is clear that this elec- 
trical polarity has been established as the controlling axis of 
development by the time all the yolk is used up. 

Our primary axis is thus fixed even before fertilization, 
but any of the infinity of meridians from pole to pole can 
apparently become the dorsal-ventral (back-to-belly) plane. 
Just how this is determined seemingly depends upon the 
influence of some aspect of the environment-perhaps, as in 
frogs, it is a matter of where the sperm enters the egg, this 
meridian becoming the mid-ventral line, and the opposite 
one the dorsal. However that may be, the fixation of this 
plane lays the foundation for bilaterally symmetrical develop- 
ment. Right and left of this plane the sides begin to develop 
as mirror images of each other. 


In general, the gradients of activity run from head to tail, 
from back to belly. The cells toward the head divide faster 
and, consequently, are smaller than those to their rear. Simi- 
larly, cells along the back divide more rapidly and are smaller 
than those ventral to them. Since the gradients are not merely 
axes, but involve cell layers and masses in the developing 
embryo, it is better to speak of the whole mass of cells influ- 
enced by any particular gradient as a gradient field. 

Next comes the localization of substances. Some are al- 
ready localized in the egg, as is the yolk. As cell division pro- 
ceeds, others are also localized, under the influence of physical 
factors such as gravity, and no doubt more especially because 
of the polarity of the embryo. These substances must include 
also the products of such genes as commence activity at this 
time or earlier. Such secondary enzymes or precursors, once 
localized, play an important part in the further development 
of form. They have been called organizers, the hormones of 

The best known of these affords a striking example. 
When the embryo has grown to resemble a sack with only a 
small opening to the exterior (for a detailed account of the 
process see Chapter V), the nervous system begins to form 
as a groove which extends from the dorsal lip of the pore 
toward the head end. This groove deepens, the walls fold 
over to make a tube, and the nervous system thus originates 
from the surface layer of the body. Now we might ask— could 
any portion whatever of the surface layer, called the ectoderm, 
do this— and make a complex brain and spinal cord? This 
question has been answered by ingenious experiments upon 
frog and salamander embryos. If the dorsal lip of the pore 
is cut away, and the tiny piece transplanted to another posi- 
tion, a groove will extend from it toward the head end, and 
shortly we can see a neural tube in process of growth. 
Or transplant these particular bits of tissue from several em- 
bryos into one, and you may produce as many neural tubes 
as you wish! Any part of the surface layer possesses the capac- 


ity to develop into a neural tube, but does so only tvhen 
stimulated by a particular organizer, which is the substance 
(or substances) localized in the dorsal lip of the pore. 

We can be sure that chemical substances, and not some 
influence of the living tissues, are responsible for this effect, 
for dead material or extracts from the same source are just 
as effective as the living organizer. 15 However, there is a 
difference in the way a transplanted dorsal lip organizer acts 
upon head and trunk. It appears, in short, that the organ- 
izer substance merely induces the surface layer of the body 
to form a neural tube, while the regional characteristics of 
the neural tube depend on the "axial gradient," or polar- 
ity, already established. 

If we delay transplanting the organizer until the surface 
layer of the host embryo has already reached a certain point 
in its normal differentiation, the organizer will have no 
power to reverse the changes that have occurred. In other 
words, the organizer acts only on cells below a certain stage 
of specialization— beyond that the chemical and physical set- 
ting of the protoplasm is no longer one in which this hor- 
mone can affect matters. Districts can be delimited which 
have become fated to form particular organs (Fig. 55, p. 194), 
each district having a polarity of its own. 

These districts are somewhat different from the gradient 
fields about the axes of polarity. The latter are based upon 
dynamic equilibriums, and the dominant regions of such 
fields can activate or inhibit at a distance. A fragment of such 
a field tends to reorganize itself so as to make a miniature 
whole. On the other hand, the districts, which depend upon 
a gradient in the concentration of some substance, are, once 
outlined, of predestined fate. They do not depend upon 
equilibriums, but upon a superthreshold concentration of a 
particular organizer. Their own polarity may be swamped 
by that of the broader primary gradient, which apparently 

is The analysis of these extracts indicates that at least some of the or- 
ganizers belong to the group of sterols. 




Hindlimb Ear NeuralTube Eye 
'Field Field /Field Field 







Fig. 55. Diagram of an amphibian embryo to show the approximate localization 
of the main districts (unfortunately labeled "fields") known from experiment. 
The arrows indicate that the districts are polarized from their first appearance. 
Hypophysis is a synonym for pituitary gland. The balancers are organs grow- 
ing on the outside of the tadpole's throat region. (Redrawn from Huxley and 
DeBeer's The Elements of Experimental Embryology. Courtesy of Cambridge 
University Press. By permission of The Macmillan Company) 

correlates the growth of different parts. Thus, if an arm bud 
(a district) is grafted onto the spot from which a leg bud 
is removed, it will develop into an arm, but its size will be 
that of a leg. It appears, therefore, that the primary axial 
gradients and their fields are responsible for the pattern of 
the organism as a whole, while the organizer-districts lay out 
the minor regions for the several organs. 

Another example of an organizer may be taken from a later 
stage in development. After the front end of the neural tube 
has developed into three bulges which will later make the 
brain, two side pouches grow from the front one, the forebrain. 
These extend until they reach the ectoderm, growing into 
the form of cups on slender stalks. If, now or earlier, this 
part of the forebrain is cut out and transplanted beneath 
the surface layer, either of the same embryo or of another of 
an age not too much older, it will induce the ectoderm to 
fold in and assist in producing an eye in the normal fashion 


(see Chapter V, pp. 289 £.). Just anywhere— for all the ecto- 
derm is potential eye material! In this way you may produce 
as many eyes as you wish, although, unless they are connected 
to the brain, they will naturally not be able to contribute 
to vision. The side pouches of the forebrain are the eye 

Hormones which have specific effects during development 
are now being discovered in abundance. Some act early in 
development, some late. There is a South American blood- 
sucking bug (Rhodnius) which can molt only at an interval 
after having had a big meal of blood. If it fails to get a real 
gorge, it consequently cannot grow or mature. The molting 
normally results from the production of a hormone by a 
gland near the brain. The hormone circulates through the 
blood and sets the epidermal cells, long quiescent, into rapid 
cell division. This hormone is effective not only in closely 
related species but even in as distant a relative as the com- 
mon bedbug, which belongs to a different family. It is, in 
fact, a general rule that hormones have similar effects on a 
wide variety of related organisms. 

Perhaps no better example than the one just described can 
be found for revealing the involvement of genes, cytoplasm, 
organismal and environmental factors in development. Here 
we behold an environmental variable (a good meal) acting as 
the trigger which sets going a localized physiological process 
that is itself an expression of hereditary potentiality. This 
physiological process is the secretion of a hormone to which 
only certain tissues of the body, the epidermal cells, are re- 
sponsive. The responsiveness is, no doubt, a matter of cyto- 
plasmic attunement. Finally, mitoses are set in motion; the 
genes in these cells are themselves stimulated to activity; 
growth takes place; a new cuticle is laid down, and the old is 
molted. The type of cuticle, whether immature or mature, 
is seemingly determined by another hormone emanating 
from the same gland as the molting hormone. 

In Drosophila, too, a molting hormone has been found. 


But more interesting in this organism are the diffusible sub- 
stances involved in the production of normal eye color, for 
these— two are known— are each dependent upon a particular 
gene (vermilion and cinnabar). One of the hormones (the 
v + hormone) appears to be a precursor of the other (the cn + 
hormone); for, while eye buds from larvae of either ver- 
milion or cinnabar genotypes become red (normal) when 
implanted in wild-type hosts, the results of reciprocal trans- 
plants of vermilion and cinnabar are different. A "cinnabar" 
host can supply a "vermilion" implant with the substance it 
lacks, and produce red eye color; a "vermilion" host cannot 
do this for a "cinnabar" implant. These two hormones have 
been extracted from various tissues, and, although not yet 
completely analyzed, it is clear that they are not proteins but 
are of a simpler chemical constitution. Probably they are 
amino bases produced by protein breakdown. They do not 
behave as enzymes. These facts make it seem likely that the 
normal eye color is, so to speak, a by-product utilizing the 
waste of some more vital process. 

Scarlet is another recessive gene affecting the eye color in 
a manner indistinguishable from vermilion or cinnabar 
phenotypes. Yet "scarlet" larvae have both the v + and the cn + 
hormones in abundance. One or the other of them must 
somehow be kept from use. Here is a single phenotype which 
can be brought about by any one of three (or more) genes, 
each having its own individual mode of action. This situa- 
tion should help us to understand the many instances in 
human heredity where a certain trait, such as hemophilia, is 
commonly sex-linked, but not always; or where, as in the case 
of congenital night blindness, a trait is a simple dominant in 
some families and in others a sex-linked recessive. 

In the mealmoth (Ephestia) and in a wasp (Habrobracon) 
parasitic upon it, there are also recessive eye colors (red and 
ivory, respectively). The normal alleles of these genes are 
also responsible for the production of eye-color hormones. 
It is a startling indication of how similar a biochemistry may 


underlie the development of distantly related forms to dis- 
cover that the known hormone in the mealmoth is the same 
as the v + hormone of Drosophila, while that of the parasitic 
wasp is identical with the cn + hormone. Perhaps the very 
genes themselves are identical, although there is at present 
no way of knowing. 

In plants, too, hormones have been discovered which play 
an important role in growth. These are the three auxins (see 
Chapter I, p. 38), some one of which is apparently present 
in every plant. They bring about the elongation of cells 
even in unbelievably small concentrations; when applied to 
only one side of a growing oat sprout, 1 mg. of either auxin 
a or auxin b would be sufficient to cause a io° bend in each 
of 50,000,000 shoots! Heteroauxin, the third of the trio, and 
already successfully synthesized, 16 is only half as potent. Aux- 
ins are formed in the growing tips of stems, buds, leaves, and 
branches, and diffuse toward the base of the plant and on 
down into the roots. Here, too, there are cells of the par- 
ticular age and character that are sensitive to the auxin, and 
even more so than those aboveground. The concentration 
which evokes maximal growth in the root cells is only about 
1/10 of that required for buds and only 1/100,000 of that 
required for stems. The result is that growth by elongation 
takes place in a root only while it is very young and tiny, 
and is soon done, before the root hairs begin to form; whereas 
stems may continue to lengthen over a much longer period. 

The response of a growing plant to light or gravity is 
also based upon the presence of an auxin. As for gravity, it 
appears that auxin tends to accumulate on the lower side 
of a horizontal stem; this side then grows faster than the 
upper, and the stem curves upward until the concentration 
of auxin becomes equal around the stem. Similarly, auxin 
accumulates to a greater extent on the darker side of a stem, 
so that it curves toward the light. On the other hand, be- 

16 All three auxins are monobasic organic acids. Heteroauxin is indole-3- 
acetic acid. 


cause of the greater sensitivity of the root to auxin, its elonga- 
tion is inhibited by the same concentration that stimulates 
the stem. A horizontal root, therefore, grows down because 
the accumulation of auxin on the lower side inhibits elonga- 
tion there more than on the upper side. In this way the 
same environmental factor acting on the same internal 
agent may yet produce strikingly different results in various 
parts of an organism because of the earlier differentiation 
of those parts. 

To see how the genes may regulate this biochemical mech- 
anism of growth control, we need only look at the dwarf 
mutant form of maize known as nana. In this recessive type 
auxin is destroyed faster than normally, and curtailed growth 
is the consequence. In man the recessive gene which pro- 
duces midgets probably acts through the endocrine glands 
in a somewhat similar fashion. 

All of the preceding instances of hormones at work in 
growth and development may help us to understand the 
still more complex nature of our own development, and the 
role of hormones in it. Because we have already devoted 
much attention to the genetic aspects of sex, the hormonal 
control of sex differentiation should make a good example. 

We may recall that in all individuals there exists a potenti- 
ality for producing the sexual characters of both sexes. All 
male organs have female counterparts, and vice versa. More- 
over, with the exception of the ducts which provide outlets 
for the reproductive cells, these corresponding organs always 
develop from the same buds. It is the direction in which 
the development proceeds, or the degree to which it extends, 
that determines final differences. The story is therefore one 
of complementary inhibitions and stimulations. 

Let us start with the gonads. As they first develop, each 
consists of an inner core (or medulla) of male tissue and an 
outer rind (or cortex) of female tissue. Each of these forms 
a hormone, which works antagonistically upon the tissues of 
the opposite sex, at the same time inducing more vigorous 


growth in the tissues of the same sex. In some way the geno- 
type (XX or XY) determines which element will get the 
upper hand, and before long the other is first inhibited and 
then commences to dwindle (see Fig. 56). In the male the 
female tissue eventually disappears completely; in the female 
a small remnant of the male issue is left, so that a female 
under certain conditions may develop intersexually. 

Ovary \ ,,.., J \ v< -Y^ 5 ^ 


Fig. 56. Diagram to illustrate the alternative development of ovary and 
testis from the same type of rudiment (upper center), consisting of both male 
tissue (M) and female tissue (F). The small arrows indicate the predominat- 
ing secretion in each case. The larger arrows indicate the tissue in the rudi- 
ment that becomes predominating in ovary and testis, respectively. (Redrawn 
from Burns, after Witschi) 

This general interaction reminds us of the man who lifted 
himself by his bootstraps— for the more hormone one element 
of the gonad secretes, the more it inhibits the other element, 
and the more it stimulates its own further growth, so that 
it can secrete still more hormone. We should like to know 
what puts a stop to this! And what is the relation of these 
two hormones to the organizers which presumably cause the 
gonad to appear in the first place? Are they the same? 

Observations upon conjoined twins of different sexes, or 
experiments, such as grafting a gonad of one kind into a 
host of the opposite sex, or castration, or the administration 
of various dosages of hormones, show us the further conse- 
quences of the interaction of these hormones. In birds and 
lower vertebrates sex may be completely reversed. In mam- 
mals this has not been found possible, but partial reversal is 
well known. AJreemartin is a genotypically female calf that, 


through conjunction of blood vessels with a male calf, has 
been subjected to dosage with the male hormone while in 
the uterus, until it has undergone partial sex reversal. The 
ovaries are destroyed early, and from then on the female hor- 
mone is lacking. This naturally has further consequences. 
The male calf is unaffected because testes develop faster than 
ovaries, and the male hormone therefore swamps the female. 

By administering hormones, we know that large doses of 
either male or female sex hormones can induce both the male 
and the female ducts to develop. In smaller doses, however, 
each sex hormone appears to stimulate only the ducts of the 
corresponding sex. That is, the rudiments of the male ducts 
are more sensitive— they have a lower threshold for response 
—to the male sex hormone than to the female; and conversely 
for the rudiments of the female ducts. 

While the sexual ducts appear to be responsive to both 
hormones, the external genitalia and the secondary sexual 
characters are, according to our present knowledge, affected 
solely by the male hormone. If you administer female hor- 
mone to a castrated animal nothing happens. But male 
hormone makes the castrate externally into a male, and will 
even modify the external sex structures of a female into their 
male counterparts. Of course, here the previous development 
as female will count for something and reversal will rarely 
be complete. The lack of any effect upon the external geni- 
talia and upon the secondary sex characters by the female 
hormone at last explains why a male fetus develops these 
structures normally in spite of the abundant female hormone 
supplied by the mother. 

A strange thing is that the germ cells themselves are not 
involved in all this. In birds, they originate elsewhere and 
make a long migration before getting to the site of the 
gonads. In mammals they may originate in the gonads, but 
only after these have accomplished a considerable part of 
their development. The gonads, and hence the other sex 


structures, will develop quite normally in the absence of 
sex cells, but the animal will, of course, be sterile. 

Our picture of sexual development in terms of hormones 
is still much too simple, 17 but its general character is perhaps 
clear enough. To sum up, at definite locations in the body 
organizers lay out the districts for the gonads and their ducts. 
Since each gonad includes both male and female tissues, prob- 
ably two organizers collaborate in inducing it to start devel- 
opment. Where these substances are first produced is un- 
certain, but they probably come to be concentrated at the 
appropriate points through the influence of the primary 
gradient fields. As the gonads increase in size, the male and 
female portions commence to elaborate their respective hor- 
mones, which are perhaps chemically the same as the gonad 
organizers. A conflict of self-stimulation and reciprocal inhi- 
bition results; and one type of tissue, that favored by the 
genotype, overwhelms the other. Its hormone stimulates the 
corresponding type of sexual duct to enlarge. Finally, if it 
is the male hormone, it stimulates the external genitalia and 
secondary sexual characters to develop differentially. 18 

The attainment of ultimate size and form by the organs 
brings us to the third major group of developmental fac- 
tors. The axes and planes of symmetry, and their gradient 
fields, lay out a ground plan of development. Organizers 
block in the details. But the ultimate form depends upon 

17 We have, for example, said nothing here about the masculinizing effect 
of the hormone from the cortex of the adrenal glands upon the external 
genitalia and secondary sex characters, or about the general control of the 
pituitary gland over the activity of the gonads. 

is For further study of these problems, the reader is referred to such 
authoritative works as: 

Huxley, Julian and DeBeer, G. R. The Elements of Experimental Embry- 
ology. Cambridge University Press, 1934. 
Spemann, Hans. Embryonic Development and Induction. Yale University 

Press, 1938. 
Allen, E., Ed. Sex and Internal Secretions, ed. 2. Williams and Wilkins, 

Baltimore, 1939. 
See also Mohr, O. L. Heredity and Disease, pp. 164-188. W. W. Norton, 
New York, 1934. 



relative growth rates. This means simply that some parts 
grow slower or faster than others. To begin with, for ex- 
ample, about three fourths of the body is laid out as head! 
Yet, since the head grows at a consistently slower rate than 
the rest of the body, two months later the head is not quite 
as large as all the rest, at birth it is about one fourth as large, 

I— 100 


k 60 














' Arms 

^^_ — - 







3 I Z 

6 Q ■ tO 12 14 t& 18 20 

Fig. 57. A, growth curves of head and neck, arms, and legs compared with 
that of the whole body to show differences in relative growth rates. 

and at maturity it is only 7 per cent of the total bulk of the 

Our limbs do not even appear until the fifth week of our 
prenatal development. The limb bones alternately lengthen 
and thicken (six months of each), and, moreover, some are 
lengthening while others are thickening. At two months our 
limbs are 6 per cent of the body's bulk, and arms and legs are 
equal. At birth, seven months later, they make up nearly one 
fourth of our body, but our legs are almost twice the size 
of our arms. (Have you ever noticed the gangly proportions 
of newborn lambs or colts? The higher relative growth rate 


of limbs before birth is evident there too, although thereafter 
the growth of their legs slows down.) At maturity our limbs 
are 40 to 50 per cent of the body's bulk, but our legs are 
three times the bulk of our arms. No wonder, then, that 
babies are so different from adults, with their heads so much 
larger in proportion to their legs. We may represent these 



5 Birth 



6 12 25 

years years years 


Fig. 57 (Cont'd). B, changes in form and proportion of the human body dur- 
ing fetal and postnatal life. (B redrawn from Morris' Human Anatomy, ed. 
9, Scammon, after Stratz. Courtesy of The Blakiston Company) 

growth rates graphically by curves showing the increase in 
bulk with age (Fig. 57). 

Organs may grow at the same rate as the whole body. As 
long as this is true, increase in absolute size is not accom- 
panied by any change in relative size. But, as we have just 
seen, other organs grow at a rate different from that of the 
body as a whole, or an organ may grow at different rates in 
different dimensions— this is the phenomenon of heterogony. 
Since it is extremely unlikely that any animal will not have 
some heterogony, it follows that all animals must alter in 
form as they alter in size. 



One of the most striking facts learned about growth is that, 
where heterogony obtains, the ratio between the two differ- 
ent growth rates remains constant for lo?ig periods during 
development. In spite of the fact that both growth rates are 

Fig. 58. Baboon skulls of various sizes, to show the increase in relative size 
of the facial region with absolute size of skull. (1) newborn; (2) juvenile (with 
milk dentition); (3) adult female; (4) adult male. (From Huxley's Problems in 
Relative Growth. Courtesy of The Dial Press) 

usually changing, for growth tends to slow down with age, 
they remain related to each other in a constant way. 19 This 

19 This can be expressed mathematically in the form y = bx k , Avhere x 
and y are the magnitudes of the two differentially growing elements, b is a 
constant indicating the value of y when x = 1, and k is the ratio of the 
relative growth rates. Since k is logarithmic, this means that growth is a 
process of multiplication of living substance and is not simply additive in 
character. In other words, the more growing material there is, the greater the 
access of fresh material. 


produces a progressive change in relative size or form. The 
final form consequently will depend entirely upon whatever 
absolute size is reached. Examples of what is meant are so 
clear from pictures that it is scarcely necessary to discuss 
them. The facial part of a baboon's cranium grows at a faster 
rate than the rest of it, and the ratio between the two growth 
rates is constant. Figure 58 shows the result. 

For many years researchers have wondered about the ge- 
netic basis of the differences between the queen bee and 
workers or between queen ant and the several varieties of 
soldier and worker ants. Then it was discovered that the 
workers were all neuter females, sterile because fed by their 
nurses on a somewhat deficient diet. Now it seems likely that 
the big-headed, fierce-jawed soldiers and the small-headed, 
weaker workers also differ only environmentally. For there 
is positive heterogony of head over body; and the larger the 
absolute size a worker attains, the bigger its head and jaws be- 
come in proportion (Fig. 59, p. 206). It is the limitation in the 
total amount of growth that is the decisive factor. Here it 
is determined by nutrition; yet in another organism it might 
equally well be genetically controlled. 

The constancy of the ratio of the growth rate of a part, 
such as a limb, to that of the whole body does not mean that 
all parts of the limb are growing at the same rate. After 
birth the hind legs or lower limbs grow more slowly than 
the body. Measurements show that the most distal joints are 
growing relatively slowest, and that there is a regular gradi- 
ent of increasing growth from there to the trunk. Conversely, 
before birth, when the legs are growing faster than the body, 
the distal parts are growing fastest. So, whether the heter- 
ogony is positive or negative (that is, whether the differential 
growth rate of the part is faster or slower than that of the 
whole), this distal region is the growth center of the limb. 

Since the growth gradients extending in the three planes 
of space from the growth center may differ, the composite 
of all growth centers and growth gradients in the body makes 



Fig. 59. Increase of the relative size of the head with absolute size of body in 
neuters of the ant Pheidole instabilis. Enlarged. (From Huxley's Problems in 
Relative Growth. Courtesy of The Dial Press) 

up a complex growth pattern. More than twenty years ago 
D'Arcy Thompson pointed out that the differences in form 
between related species, even when extreme, might be inter- 
preted as simple changes in the location of growth centers 
or in the relative magnitude of growth gradients. Thus the 
astounding shape of the great ocean sunfish may be derived 
from that of an ordinary-looking relative merely by distorting 
in a perfectly regular way Cartesian coordinates drawn about 
the figure of the latter (see Fig. 60). The sunfish has evi- 
dently acquired, over and above the growth pattern of its 
relatives, a sharp growth gradient running from a growth 
center at the tail toward the head. 



12 3 4 5 6 

Fig. 60. Cartesian transformation of the outline of the fish Diodon to give 
the outline of the related sunfish Orthagoriscus. (From Huxley's Problems in 
Relative Growth. Courtesy of The Dial Press) 

This is also illustrated in the formation of at least some 
human embryo monsters. In the first one shown on page 208 
(Fig. 61 A), there is marked underdevelopment of the head, 
accompanied by greater growth of the next posterior region of 
the body gradient. Hence the chest is enlarged, and a growth 
gradient runs from there out the arms, with progressively less 
increase over normal in upper arms, forearms, hands, and 
digits. In the second case (Fig. 61B) there is a relative increase 
in the potency of the growth center in the head, and a steeper 
gradient along the body axis. 

Numerous are the instances of gene-controlled relative 
orowth rates. The short limbs of dachshunds and basset- 
hounds are due to a single recessive gene in each case. The 



"short-ear" gene in mice produces localized changes in the 
growth of the skull. In squashes and gourds there are genes 
for both size and shape, the latter controlling relative growth 
rates, so that the shape of each fruit changes progressively 

during its increase in size. 

Fig. 61. Graded growth effects in two human monsters. In A, the normal 
infant is shown in outline, the monster is shaded; in B, the normal infant is 
shaded, the monster is shown in outline. For further explanation see page 207. 
(From Huxley's Problems in Relative Growth. Courtesy of The Dial Press) 

If, on the one hand, the relation of relative growth rates 
to genie control is apparent, it is no less clear that they must 
also be related to the primary axes, to the delimited fields 
and districts, and to the hormones. In regenerating hydroid 
polyps the first region to differentiate acts as a dominant 
region controlling the development of the rest of the body. 


Moreover, the location of this dominant region can be al- 
tered by external factors which either temporarily over- 
whelm the primary axial gradient, as an opposed electrical 
gradient can do, or completely wipe it out, as do weak poi- 
sons. Here the production of form during growth, a matter 
of local differences in growth rates, is clearly subject to the 
larger, fundamental growth pattern of the whole. 

If you transplant an organ from a slow-growing salamander 
to a fast-growing one, it will continue to grow slowly. Con- 
versely, if you transplant an organ from a fast-growing sala- 
mander to a slow-growing one, it will maintain its own 
inherent growth rate. This shows that the localized growth 
centers and gradients are related to the districts of the em- 
bryo induced by the localized concentration of organizer 

Finally (1) the distinctive growth of the sex organs in male 
and female under the influence of the sex hormones, (2) the 
preponderant stimulation of limb growth in pituitary gigan- 
tism, and (3) the action of thyroxin in stimulating the growth 
of internal organs (heart, lungs, liver, kidneys, spleen, adre- 
nals, pancreas) while suppressing that of the pituitary gland— 
these show the relation of hormones to relative growth rates. 

A further aspect of heterogony which particularly con- 
cerns us is the appearance of asymmetry on the two sides of 
our body. In all the higher, bilaterally symmetrical animals 
the later phases of growth show some degree of secondary 
asymmetry. Our stomach projects toward the left, and heart 
and intestines are spirally coiled. Dentition and facial fea- 
tures are somewhat asymmetric, and the crown-whorl of our 
hair spirals in a particular direction. One side of the brain 
also achieves a functional predominance over the other. All 
these seem to be due to the existence of growth gradients 
running from left to right, the most active growth usually 
being on the left. These in turn may be due to gradients in 
the distribution of auxin-like substances, for, if you cut out 
a piece of the roof of a tadpole's gut before its coiling com- 


mences and replace it after reversing it 180 degrees, the in- 
testine and heart will coil in the opposite direction to their 
usual one, and the stomach will also be reversed in position. 
Studies on the coiling of snails and other mollusks show that 
their asymmetry is already determined in the egg before fer- 
tilization. Moreover, it is determined by a single pair of 
alleles present in the mother. 20 In our own case, too, the de- 
velopment of left-handedness or right-handedness is pre- 
dominantly determined by a single pair of genes. The greater 
frequency of right-handed people indicates that, because of 
the crossing of the nerve pathways in the brain-stem, most 
of us are left-brained. In other words, the dominant allele 
renders the left end of the growth gradient for the brain 
predominant; the recessive allele favors the right end. If it is 
permissible to put together this evidence assembled from 
different organisms, we have here a clear chain starting from 
the genes, and leading through concentration gradients of 
growth substances to the appearance of left-right growth 
gradients which finally result in phenotypic asymmetry. 21 

One more feature of development deserves a word. The 
early phases of the development of any structure as a rule 
take place before it begins to be of any use. Eventually it 
passes from this prefunctional stage to one of use, and this 
use definitely affects the further course of its development. 
We are all familiar with the stimulating effect of exercise 
upon the growth of our muscles, but it goes much further 
than this. The pull of the muscles orients the fibers of the 
attached tendons along the lines of stress. The finer archi- 
tecture of the bones— the direction of the spicules and tiny 

20 This implies that the paternal contribution to the genotype as regards 
this pair of genes is delayed a full generation in its effect, for a dominant 
gene from the father will not determine the direction of coiling in the 
immediate zygote but in the eggs produced by that zygote after it has 
developed to maturity. 

21 Classic reference on the subject of heterogony is Problems in Relative 
Growth by Julian Huxley (Lincoln MacVeagh, the Dial Press, New York, 


struts which provide the spongy structure at their ends, and 
the denser, firmer structure in their shafts— this, too, depends 
on the direction of the stresses they meet. Anyone who has 
ever seen the wasted, bent legs of an invalid, or who has seen 
an x-ray picture of their curved, weakly bones, will know how 
great this effect can be. Use of the muscles and organs also 
determines the amount of their blood supply, and this plays a 
great part in fixing the number, size, course, and branch- 
ing of the minor blood vessels. The severity and type of 
bacterial invasion regulate the total number and the rela- 
tive frequency of the several sorts of white blood cells. Lack 
of sufficient iodine in the diet will cause the thyroid gland 
to hypertrophy, resulting in a goiter; and removal of one 
kidney will result in the enlargement of the other, which has 
to do double service. Even the character of the cells may 
be changed by use, as in one instance where the artificially 
induced hypernormal use of the urinary bladder in a dog 
caused the walls of this organ to become ten times thicker, 
the cells took on a striated character like that of heart mus- 
cle, and the whole organ pulsated rhythmically. 


At the beginning of this chapter we examined the problem 
of fat color in rabbits, and concluded that the potency of 
either heredity or environment can be discerned only when 
we isolate the effects of either one of them by rendering the 
other constant. We may see how easy it is to overlook the 
implications of this principle from the fact that, until re- 
cently, books on human heredity classified pellagra as a he- 
reditary disease because it "runs in families," ignoring the 
fact that faulty nutrition (in this instance lack of nicotinic 
acid) is also shared, like many other aspects of environment, 
by those living under the same roof. Yet, with this clearly in 
mind, we must still face the practical aspects of our question. 


Should we put our trust in eugenic measures, or should we 
work for a better future by improving our environment? 

Now this is not to be confused with the old, erroneous 
distinction between hereditary and environmental traits. 
Rather, we are here concerned with four categories of rela- 


Genetic differences 
manifested in prac- 
tically all types of 

Genetic differences 
manifested only in a 
restricted range of 

Differences due to en- 
vironment manifested 
only in a restricted 
range of genotypes 

Differences due to en- 
vironment manifested 
in practically all 


Categories (1) and (4) are the indisputable cases, such as the 
differences between color-blind or albino and normal, in 
the first; and between one who has accidentally lost an arm 
or an eye and one who has not, in the fourth. These two 
categories, however, include relatively few examples of dif- 
ferences. For instance, there is little besides mutilations in 
category (4). Categories (2) and (3), on the other hand, are 
extensive and include most of the traits we would like to 
control,, and may possibly be able to. 

There is, of course, a gradual transition from category to 
category. It is especially important to realize that different 
categories frequently include the same phenotype; that is to 
say, exposure to a particular environmental factor at a particu- 
lar time during development will very likely produce an effect 
like that of some known gene mutation. Thus the phenotype 
of genetic rumplessness in chickens has been duplicated by 
treating eggs with abnormal temperatures during the first 


week of their incubation. So, too, cretinism may appear in 
many genotypes, wherever the local supply of iodine is low; 
or, where the supply is adequate for the majority, it will ap- 
pear only sporadically, in the few most susceptible genotypes. 
In the first kind of locality we might regard cretinism as en- 
vironmentally caused, while in other regions it would appear 
to be hereditary. The fundamental fact, however, remains 
the same. Various genotypes have a differential susceptibility 
to lack of iodine; and this, along with the local abundance 
of the element, determines the incidence of cretinism. 

An example that we can treat graphically may further 
help us to understand this point. In Drosophila, the number 
of facets in the eye is reduced below normal by the gene 
Bar and still more by its allele Double-Bar. The number 
of facets is also decreased by any increase in temperature 
during the susceptible period of eye development. However, 
the two Bar alleles do not act proportionally at different 
temperatures. The change in the effect of Bar with a shift 
in temperature of nine degrees is much greater than that in 
the effect of the Double-Bar allele. If the effect of the genetic 
difference is taken as the difference between the eye size 
in the two stocks at any one temperature, it is obviously 
greater at 16 C. than at 25 C. (Fig. 62). If the effect of the 
environmental difference of 9 (not the total environmental 
effect) is regarded as the difference in eye size at the two 
temperatures in any one stock, it is clearly greater for the 
Bar stock than for the Double-Bar stock. Then, of the dif- 
ference between the largest eyes (Bar at 16 ) and the smallest 
(Double-Bar at 25 °), there is no single answer as to the rela- 
tive potency of genes and environment. At 16 the genes 
have it; at 25 the major role is that of the temperature 
difference. For every combination of each environmental 
change and each genotype, the relative potency must be as- 
sessed individually . 

These examples throw the emphasis back on the biochemi- 
cal chain-reactions which lie between genotype and pheno- 



type. The greater our knowledge of these becomes, the more 
readily we can correct for genetic inadequacy by appropriate 
environmental change. It is a simple matter to feed salts of 
iodine in correct dosage to those who need it, or to step up 
resistance to a disease in susceptible genotypes by vaccination 

Fig. 62. Diagram showing the change in the eye size of Bar and Double-Bar 
Drosophila with changing temperature. E = change due to shift of 9 C. 
in Bar; E' - change due to shift of 9 C. in Double-Bar; G = difference due 
to genotype at 16 C; G' - difference due to genotype at 25 C. (From data 
of Krafka) 

or serum treatment. This should make it clear that artificial 
selection and environmental control are, after all, not alterna- 
tives between which we must choose. The former is a treat- 
ment applied to the genetic pattern of a population. The 
latter is a treatment applied to the phenotype of an indi- 
vidual. Both can be used in the same instance, and the ad- 
visability of applying them should be considered separately. 
The efficacy of eugenic measures is not the. issue just here. 
What is pertinent is the constant possibility that, by acquir- 
ing sufficient knowledge of the way in which a trait develops, 
we can achieve control over it. To say that hemophilia 
and Huntington's chorea are hereditary diseases does not 


mean that they are incurable. It simply means that our re- 
search on them should be directed into channels other than 
those of bacteriology. 

We need to learn more completely the susceptibility of 
each trait to environmental modification. We need to learn 
what factors are normally variable, how much, and when. 
In our search for limiting factors, we must distinguish more 
carefully between uterine environment, familial environ- 
ment, and general social environment. 

It would appear well-nigh impossible to secure a suffi- 
ciently homogeneous environment for the study of the effects 
of genetic differences in man. Even with our experimental 
animals the problem causes constant difficulty. Only the uter- 
ine environment and those characters which complete their 
development within it offer some hope. The principal varia- 
tions in the uterine environment are nutritive, and the simi- 
larity of the rat's nutritive requirements to ours, and the high 
degree of genetic homogeneity in the rat stocks now used 
for experiments afford a substitute for experimentation upon 
ourselves. Yet the accompanying list of the nutritive sub- 
stances (Table III, p. 216) known to be limiting factors is ex- 
tensive, and their combinations would be practically limitless. 

Fortunately, nature has furnished us another means of 
isolating the effects of heredity and environment. Although 
"it is impossibl e to h o pe for completely identical or absolutely 
different environments, or for completely different heredities, 
we can obtain identical heredities. Identical twins have de- 
veloped from the same original zygote. Their genotype being 
identical in all respects, any differences between them must 
be~cTue to environmental factors. The converse, however, 
that their similarities are entirely due to their genetic iden- 
tity, is an error we should beware of, for they have also expe- 
rienced the same uterine environment; 22 generally they have 

22 Just what differences can exist in the uterine environment is clear 
from the fact that "Mongolian" idiocy, which is perhaps a Mendelian reces- 
sive, finds expression principally in infants born very late in the mother's 
childbearing period. In other words, the conditions within the same womb 



Amino Acids 

Cystine or methionine 









An unsaturated fatty 
acid (such as linoleic 
acid) (vitamin F?) 

Table III 

Minerals Vitamins 

Calcium A (or precursor carotene) 

Chlorine B x (thiamin) 

Copper B 2 (riboflavin) 

Iodine avidin 

Iron biotin (vitamin H) 

Magnesium choline 

Manganese folic acid 

Phosphorus inositol 

Potassium nicotinic acid (pellagra 

Sodium preventative) 

Sulfur pantothenic acid 

Zinc para-amino benzoic acid 

B 6 (pyridoxine) 
C (ascorbic acid) 
D (calciferol) 
E (antisterility) 
K (antihemorraghic) 
L 15 L 2 (liver filtrate) 
P (citrine) 

grown up together in the same family; and, being of the 
same age and sex, they are often inseparable companions, 
so that they fall naturally into as similar social environments 
as can be. What we really want to know is the answer to 
the question: How different can identical twins become after 
exposure to measurable differences of environment? 

Of all the studies of identical sibs that have been made, 
few include any instances of their separation, particularly 
during the formative years. Some years ago Johannes Lange, 

in a woman's prime and later when approaching menopause are sufficiently 
different to settle whether or not this affliction will manifest itself. As for 
identical twins, two or more other factors enter in. The fusion of their fetal 
blood vessels may result in inequalities in their nutrition. The asymmetry 
mechanism of the single individual is disturbed by its partition between the 
two, and a considerable frequency of mirror-imagery between one-egg twins is 
the consequence. Differences in position and pressure may also play some role. 
These several factors may be sufficiently potent to account for those slight 
differences in such characteristics as height, weight, head shape, and intelli- 
gence which even identical twins exhibit. 


of Munich, made a very interesting study of twins with 
criminal records. 23 He examined thirty pairs of twins, in 
each of which one member had been imprisoned. Thirteen 
of these pairs were identical and seventeen were fraternal 
and like-sexed. Upon investigation, it turned out that in 
ten of the identical pairs the other twin had been imprisoned 
too; while in only two of the fraternal pairs was this true. 
Moreover, the case studies showed that in practically every 
instance the crimes committed by identical twins were simi- 
lar in nature and arose from resemblances in talents, sexual 
tendencies, weak will, or alcoholism. The conclusion that 
crime is Mthe unfortunate destiny of some individuals is weak- 
ened, however, when we consider once again the close simi- 
larity of the environments of two identical twins. 

Among these twins there was one pair, the Schweizer twins, 
Ferdinand and Luitpold, who were reared apart from the 
age of eight under considerably different conditions. Luit- 
pold received affection and good care, but showed himself 
irresponsible and ungrateful both toward his foster parents 
and at school and, later, in marital relations. Ferdinand was 
badly treated and severely disciplined by his foster parents, 
and did well in school. Then he ran away to his grandmother, 
who was hopelessly indulgent, and thereafter he showed him- 
self completely irresponsible and immoral. Luitpold later 
married a woman of domineering will and energy who man- 
aged to keep him at regular work and away from bad com- 
panions, and under restraint he has become "goodnatured 
and tender, generous, and socially agreeable, popular, cheer- 
ful, and musical. As a husband he is most considerate. He is 
so sentimental that he often cries in church." 24 But withal 
his wife does not trust him. The brothers clearly share per : 
sonalities very much alike, and require rigid discipline to 
supply the defects of their own weak will-power and irrespon- 

23 Lange, Johannes. Crime and Destiny. Boni Paper Books, New York, 

24 Op. cit., pp. 162-163. 


sibility. Evidently the differences in their environment have 
not created any marked difference in them in this respect, 
although their fate as adult citizens shows such a. striking 
contrast. Yet we wonder about the common influences of 
their first eight years— are not these years, after all, the most 
important ones in the development of personality and char- 

The most recent and extensive survey of our problem 25 
is a summary of studies of fifty pairs of identical twins reared 
together, fifty pairs of like-sexed fraternal twins reared to- 
gether, and nineteen pairs of identical twins reared apart. 
Of the latter, seventeen pairs were separated before eighteen 
months of age, one pair at three years, and one pair at six. 
The degree of separation ranged from complete to one in 
which the twins lived a few miles apart and attended the 
same high school for three years. Five judges rated the en- 
vironmental differences as moderate for fifteen pairs, extreme 
only for four pairs. 

When identical twins reared together are compared with 
those "reared apart— a comparison suited to measure the 
potency of environmental differences^phyjkaXjraits such 
as finger-ridge count, stature, head measures, and weight 
are found to be least affected by the environment; intelli- 
gence, somewhat more; educational achievement, still more; 
and personality or temperament, most of all. Of course, to 
someLexleiit this seriation is due to the fact that our measures 
of these traits become less valid in the same order. Yet it 
is significant that the estimated degrees of difference in the 
environments were found to be strongly correlated with the 
scores of the twins. For example, estimated differences in 
schooling were correlated with measures of educational 
achievement to the extent of .91; differences in schooling 
were correlated with intelligence somewhat less. 

When identical twins reared together are compared with 

25 Newman, H. H., Freeman, F. N., and Holzinger, K. J. Twins: A Study 
of Heredity and Environment. University of Chicago Press, 1937. 


fraternal twins reared together-this time the potency of 
hereditary differences is being measured — the greatest differ- 
ences are found in the physical traits, and the sedation is 
asTn the preceding comparison but reversed in order. The 
relative potencies of heredity and environment in the two 
sets of comparisons are in fact just the reciprocals of each 
other. This means that we can never find a fixed ratio that 
will apply either to all traits or to all conditions. It is only 
possible to determine the degree of difference that a single 
change in an otherwise common environment can make in 
a particular trait developing in a particular genotype. It 
would be possible, for instance, to take the Dionne quintu- 
plets— who are almost certainly identical— and in their other- 
wise remarkably similar environments determine the effect 
of supplying some of them, but not the others, with an excess 
of vitamins A, B v C, and D (or any four) as compared with 
the amount the average child gets. An^Jinding, however, 
would be true only for their particular genotype and their 
"standard" environment; and the experiments would need to 
be~repeated on many sets of identical sibs before valid gen- 
eralizations could be drawn. This is a dream for some Utopia, 
where all identical sibs would, because of their unique value 
to society, be reared as wards of the state. 

Meanwhile our study suggests that the relative potencies 
of heredity, and environment depend largely on the compara- 
tive magnitude of the genetic and environmental differences 
in each particular situation. When the genetic difference is 
large and the environments are similar, the genes are mainly 
"responsible for the result. When the genetic difference is 
slight and the environmental large, the influence of the latter 
predominates. No doubt this is a truism. Yet by continuing 
such studies until far larger numbers of cases have been col- 
lected, we may at last arrive at a statistically reliable estimate 
of the extent to which our various environments, as they are, 
contribute to the nongenetic differences of our population. 
And this will surely be worth while. 


This chapter has dealt solely with the inextricable charac- 
ter of the roles of genes and extrinsic factors in the course of 
development. It now remains for us to trace that course, 
reading into it, as we go along, this biochemical and bio- 
physical substratum we have just reviewed. 


From Potentialities to Realization 

BEFORE launching into the complexities of human devel- 
opment, certain general principles that will aid in un- 
derstanding its character need to be made clear. In the first 
place, development is a progress toward greater effectiveness, 
brought about through an increase in the number of associ- 
ated life-units and by a division of labor among them. Con- 
comitantly, their mutual dependence increases. They must 
submit to a loss of independence in order to become welded 
into an organism. The several steps in this process include 

(1) growth, through an increase in cell number by mitosis; 

(2) cell movements, important in modifying form and organi- 
zation; (3) cell differentiation and specialization, leading to 
the production of tissues; (4) the combination of tissues into 
organs; and (5) the correlation of parts and their integration 
into a working organism. 

As pointed out in Chapter IV, the course of development 
is determined by the interactions of genes with one another 
and with their cytoplasmic environment, which is in turn 
subject to the stimulation of the external environment. Now 
in the course of development there is instance after instance 
where foresight appears to be exercised. Structures develop 
ahead of the need for them; they have reached a functional 
level before there is a demand for their functioning. Eyes 
develop in the total darkness of the mother's womb, hands 
and feet attain their form and structure before manipulation 


or support are needed, kidneys develop while wastes are still 
effectively disposed of otherwise, and lungs are ready for 
breathing air at birth, although of no use beforehand. How 
can this be explained without attributing foresight to mere 
chemical substances, assuredly all that genes are? 

Genes, it may be recalled, are subject to mutation, and the 
majority of all mutations are detrimental. Sufficiently dam- 
aging changes weed themselves out; their possessors never 
reach maturity, never leave offspring. Even less deleterious 
changes, if they lower viability or fertility, will in time disap- 
pear from the population, or be held to a low frequency. 
The result, as Charles Darwin pointed out in The Origin of 
Species by Natural Selection, is that hereditary types which 
show superior adaptation to their environments will tend to 
survive. In modern terms, most of the genes present at any 
given time in the individuals of a species are those that have 
stood the test of natural selection throughout numberless 
generations. Only such systems of genes as would lead to the 
complete development of mature individuals, capable of pro- 
ducing offspring, would ever be able to insure their own 
continuance. All others become extinct. The adaptive char- 
acter of life is therefore to be explained neither by an inher- 
itance of acquired characteristics nor by the foresight of 
gene-molecules; it is the product of natural selection. Never- 
theless, the semblance of foresight in development is there, a 
semblance of plan and purpose. Only by keeping the action 
of natural selection constantly in mind is it possible to avoid 

A corollary of evolution by mutation and natural selection 
is that related species possess a common fund of genes, in 
addition to those other genes which differentiate them. The 
more closely related the species are, the more genes they will 
possess in common. In terms of development, this means 
that all organisms of common ancestry start their develop- 
ment in much the same way. The developmental patterns of 
the remotely related diverge first, those of the closely related 


remain parallel up to late stages. Conversely, we recognize 
these similarities in structural and developmental pattern- 
these homologies, as they are called-as evidences of common 

All related organisms tend to pass through similar levels of 
complexity in organization. However, since mutations are 
not limited in their effects to adult stages, the larval or em- 
bryonic stages may also come to differ. Only those aspects of 
development upon which vital later steps depend are so fun- 
damental that any gross modification of them would neces- 
sarily prove fatal. In spite of the modifications, then, the 
general levels of organization through which related organ- 
isms pass in the course of their development are recognizably 
similar. Development may be likened to a great highway 
upon which all organisms start out together. The highway 
forks into roads, the roads into paths, the paths into faint 
trails. First in crowds, then in smaller groups, and finally one 
by one, the other organisms leave us. Some wander off up 
other routes of specialization than ours. Others halt at some 
particular stage of the journey, making only minor special- 
ized adaptations for carrying on their lives successfully at this 
level of development. 

The latter types have long been of profound interest to 
biologists. A series representing the major levels of animal 
organization customarily forms the backbone of courses in 
zoology. The Ameba, the Hydra, the flatworm Planaria and 
the roundworm Ascaris, the common earthworm Lumbricus, 
and-among chordates and vertebrates-the lancelet Amphi- 
oxus, the lamprey, the dogfish and the frog, the reptile (or 
the chick) and the cat— these form a classical series exempli- 
fying different levels of organization from one-celled proto- 
zoan to mammal. When it was discovered, in the last cen- 
tury, that man and other mammals in their individual 
development pass through a similar series of developmental 
levels, the study of these types became of added interest. 
It is, of course, true that none of these modern forms rep- 


resents exactly either a level of our own development or any 
particular ancestor in our human lineage. Nevertheless, a 
study of their more general features will serve to clarify many 
peculiarities of our own course of development. Whatever 
develops at a more complex level is necessarily a modification 
of the organization characteristic of the simpler level. As a 
consequence, some structures appearing during development 
seem to be entirely useless— merely "reminiscent of ancestral 
conditions"; certain other parts, of use to the embryo, are 
later replaced by more effective organs in the adult. Struc- 
tures of both these types may either disappear or may persist 
throughout life as vestigial organs. Nearly two hundred of 
the latter have been listed for man. Organs of a third group 
abandon their ancestral function, are retained in the adult 
either with or without modification, and acquire new func- 

Since the ancestors of the human species are extinct, we are 
forced to rely on these modern forms to illustrate the effec- 
tiveness as well as the limitations of the particular levels of 
organization characteristic of our own individual develop- 
ment. At appropriate points, then, these forms will be intro- 
duced for the sake of comparison, in the belief that such 
studies are of real value in enabling us to understand the 
character of human development. 


The earliest phase of growth and development does not 
itself result in any division of labor— not, at least, in any that 
is visible. But it does lay the groundwork for a future divi- 
sion of labor. Repeated cell divisions result in a multiplica- 
tion of the units (cells), prerequisite to any elaborate division 
of labor. As long as the individual is comprised of only one 
cell, the zygote, this one cell must carry on all the essential 
life activities. The more cells an individual becomes divided 
into, the greater the potentiality for specialization. 


The principle works out just as it does in human society. 
An isolated man must carry on all his essential activities by 
himself, and these take so much of his time and effort that 
he has little left for nonessentials. In larger, yet still isolated 
communities, the division of labor can be carried out to some 
extent. Finally, a national or international group, with its 
highly specialized division of labor, has such efficiency that 
all essentials can be cared for by the labor of a minority. 

Cell division during development is regularly mitotic. 
Mitosis provides every cell with chromosomes which are 
duplicates of those in the parent cells. Every cell thus gets 
its full diploid quota of genes, made up of the set originally 
brought in by the sperm and the set present in the egg. No 
matter how different the various body cells come to be 
through specialization, they are, with rare exceptions, all 
alike in their genes. They have the same hereditary pattern, 
a likeness which is the foundation of coordination among 

This fact raises a serious problem, however. If all the cells 
carry the same genes, what makes them develop differently, 
one becoming a muscle cell, another a brain cell, another 
a liver cell, and so on? This question represents one of the 
major unsolved problems of embryology. The answer, as 
considered in Chapter IV, appears to lie in the interaction of 
the genes with their environment. The genes alter the char- 
acteristics of the cytoplasm, and localized differences in the 
cytoplasm then control the further action of the genes. For 
example, some of the pigment-producing genes act earlier 
than others during development. The secondary enzymes 
they produce may be so localized in the cell that a later cell 
division will distribute them very unequally to the new cells. 
There is clear evidence that this happens. 

Materials, especially the stored food (yolk), are unequally 
distributed in the egg. The nucleus and most of the cyto- 
plasm are at one end (the animal pole) and the yolk is at the 
other (the vegetal pole). When the egg is maturing, the cells 



produced are very unequal in size, as you may recall. This is 
because the spindle is oriented perpendicularly to the sur- 
face of the egg, and the cell formed at the outer end of the 
spindle is cut off with just a nucleus and a little cytoplasm. 
It is a polar body. Such a division results in keeping all the 
stored food, so necessary for the growth of the embryo, in one 



Fig. 63. Characteristic orientation of the spindle in eggs. A, at meiosis; B, at 
the beginning of cleavage. 

cell. At the beginning of embryonic growth, however, the 
problem is quite a different one. Each of the early cells re- 
quires an adequate share of stored food and other substances. 
In eggs with a small or moderate amount of yolk, the first 
spindle is ordinarily oriented parallel to the cell surface, and 
the plane of division thus passes from animal pole to vegetal 
pole, effecting an equal division (Fig. 63). 

The plane of the second division also runs from the ani- 
mal pole to the vegetal, but at right angles to the first. The 
plane of the third division is at right angles to the first two, 
which means that it is approximately equatorial. These 
three divisions produce eight cells (Fig. 64). 

Cleavage continues, with the cells becoming smaller and 
smaller, until, after six or seven successive divisions, the 
human embryo is a little ball of tiny cells, all together no 
larger than the one original cell. Up to this point there has 
been practically no growth— that commences later. Cleavage 
has merely portioned out the various substances present in 
the egg. The divisions have been leisurely, four to twelve 



hours apart, so that the berry-like embryo is now about two 
days old. 

- ' 'Sifc 

Fig. 64. Cleavage of the living monkey ovum (photomicrographs by Lewis 
and Hartmann; magnification about 180 diameters). A, two-celled stage (30 
hours after ovulation), showing polar bodies and unsuccessful sperms. B, 
four-celled stage (38 hours after ovulation). C, eight-celled stage (50 hours 
after ovulation). (From Arey's Developmental Anatomy. Courtesy of W. B. 
Saunders Company) 

At some stage in this process, as we know from other 
animals, the cells begin to lose their independence. This 
may be earlier in one species, later in another. It can be 
demonstrated in a simple way. If the cells are separated from 
one another, either experimentally or accidentally, while 
there are still just a few (four or even more), each of these iso- 
lated cells possesses all that is ne cessary to go ahead and de- 
velop into a complete individual. [ Since a ll such isolated cells 
that originate from a single zygote carry identical hereditary 
patterns, they develop into individuals that differ only by rea- 
son of exposure to varying environmental conditions. They 
are identical twins, triplets, quadruplets, or quintuplets, de- 
pending upon the number of isolated and surviving cells. 
Some time later, however, separation of the zygote into single 
cells, or even into groups of cells, will result in only partial 
development. Half-embryos and other monsters arise, strug- 
gle along for a while— then perish. The parts of the embryo 
have become dependent upon one another and, when sepa- 
rated, cannot supply their respective deficiencies. The prod- 


ucts of some of the early-acting genes have already been 
localized, and it is too late to begin over. 

In short, even before there is any visible differentiation 
among the cells, there are clear signs that they are no longer 
independent of one another. They have acquired different 
potentialities. The division of labor, though as yet invisible, 
has begun. 

This may be illustrated among some of the more lowly 
organisms, which never get beyond these early stages in de- 
velopment. In Chapter I we traced the increasing division 
of labor in the green algae of the Volvox family. There we 
saw that, as the number of cells in the cell cluster or colony 
increases, they lose their independence. First, their freedom 
of movement is sacrificed; then, by division of labor, some 
become solely vegetative (somatic) cells, others retain the 
capacity to reproduce. 

Cleavage further reinforces the nuclear control over the 
activities of the cytoplasm. Since by cell division the nucleus 
is multiplied many fold, while the cytoplasm remains prac- 
tically the same in volume during cleavage, the ratio of 
cytoplasm to nuclear material in each cell drops tremendously 
(from about 400 : 1 to about 7:1). 

Finally, there has been a tremendous increase in the pro- 
portion of surface to volume, for the volume is still what it 
was to begin with, but each of the several hundred tiny cells 
in the embryo now has a full surface of its own. Let us not 
forget that the surface of a cell, its membrane, in other words, 
is the gateway through which all substances enter or leave 
the cell. The volume, on the other hand, represents the 
amount of living substance which must be nourished. The 
relation between them is, therefore, of enormous importance, 
as we have already seen in our study of mitosis. Since, dur- 
ing the growth of a cell, its volume increases very much 
faster than its surface, the cell must soon reach a limit at 
which its membrane cannot transmit substances fast enough 
to maintain the protoplasm within. 


Various solutions to this problem have been found. Ir- 
regularities in the shape of cells are quite general and increase 
the surface area without changing the volume. An ameba, 
with its irregular shape, furnishes a good example. On the 
other hand, permanent shape and more or less streamlined 
form are necessary for rapid locomotion, and a groove or 
two are the only increases of surface that such speedy one- 
celled organisms as Paramecium are provided with. A few 
one-celled plants, able to get along without much move- 
ment, have solved the difficulty by acquiring a shape in which 
all their protoplasm is spread in a thin layer about a great 
cavity filled with sap. These are the largest of all cells, aside 
from yolk-crammed eggs-but the shape has its disadvantages. 
By. far the most general outcome of the surface-volume 
problem is cell division. It may be combined with any of the 
previously mentioned devices, for many cells in complex or- 
ganisms are very irregular in shape— nerve cells, for example 
—while plant cells are quite generally hollow, with a thin 
rim of protoplasm around a great vacuole full of cell sap. 
But the principal advantage secured by cell division— the 
multiplication into distinct units varying in their content of 
localized substances and hence capable of diverse specializa- 
tion—makes it the nearly universal basis of growth, as we 
have found it to be of reproduction. 


As the number of cells in the tiny spherical embryo con- 
tinues to increase, and the cells consequently become smaller 
and smaller, some naturally are internal in position. These, 
to be sure, have no lack of food, for an adequate supply has 
been stored up for all. On the other hand, an internal posi- 
tion is unfavorable for access to oxygen, and would make 
difficulties in the elimination of wastes. Distribution through 
cells is difficult, relatively slow, and inefficient. 

The next change in the mode of development provides a 


solution for this difficulty. Almost from the beginning the 
inner cells begin to move outward and to assume more 
favorable locations near the surface of the sphere. (It is now 
called a blastula) 

This change has several consequences. In the first place, 
it leaves the center of the embryo hollow. The cavity is 
filled with fluid absorbed by the embryo from its surround- 
ings as rapidly as it grows, and this fluid forms an admirable 
means for the distribution of materials, since diffusion and 
convection through it are far more rapid than in cytoplasm 
itself. In the second place, the movement of the inner cells 
produces an increase in the size of the ball. Thus growth 
begins— with an outward movement of the inner cells pro- 
duced by division, and a rapid imbibing of water to fill the 
middle vacancy. 

What is the advantage of this type of organization over 
that of the solid mulberry-like form? A more adequate provi- 
sion of materials from the environment to the cells and a new 
inner fluid-filled cavity enabling distribution to take place 
on two surfaces instead of only one— yes, these are obvious, 
and the capacity for further growth is itself dependent on 
them; for, as we have seen, it is limited primarily by the ratio 
of surface to volume, that is, by the problem of distribution. 
The blastula is capable of further growth, more cells can be 
maintained, and there is a corresponding increase in the 
capacity for specialization. 

We can see how this works out in Volvox (Fig. jE), which 
is characteristic of the developmental level of the blastula. 
Each individual on the surface of the hollow ball, which at- 
tains the size of a pin's head, rather closely resembles the 
individuals making up the colonies of its simpler relatives 
(Fig. 65). Each has two whiplike flagella, and green chloro- 
plasts enable it, like other plants, to synthesize its own food. 
Each cell is thus nutritively independent of all others in the 
group, but is bound to them by the jelly-like secreted capsule 
which makes up the envelope of the hollow ball. Moreover, 


y Cell- 

Cell ~~ 

Fig. 65. Part of a globular Volvox colony, to show vegetative and repro- 
ductive cells. 

each cell sends out projections which make contact with 
those of neighboring cells and enable communication to take 
place. We have already noted that the reproductive capacity 
is yet further restricted than in simpler relatives. 

Here we can add coordination to the growing dependence 
and the correlative division of labor among the cells seen in 
the simpler members of this group of algae. The more funda- 
mental life activities, nutrition, respiration, excretion, and dis- 
tribution, we shall find, are surrendered to specialization last 
of all, and even then but incompletely. Every cell carries on 
a certain amount of this generalized metabolism. In the blas- 
tula itself there is no evidence of cell specialization at all. 

At this level of organization, or earlier, we are forced to 
consider the question of individuality. Just when does the 
mutual dependence of associated cells become so great that 
we should cease thinking of them as separate individuals, 
and begin to consider them as units in a greater whole, the 


The change from a cluster or colony of individually com- 
plete units, as in the four-celled embryo or the simpler algae 
of the Volvox family, into an individual made up of special- 
ized and mutually dependent cells, as in the blastula or 
Volvox, is a gradual one. To set at any particular point the 
transition between the colony of distinct individuals and the 
larger organism must be arbitrary. Volvox, for instance, 
we may consider equally well as a colony of one-celled algae 
or as an organism of relatively unspecialized cells. 


There is a striking analogy between this situation and the 
relation between each of us and our social group. We insist 
on regarding ourselves as individuals, although human cul- 
tural development has long passed the stage when people 
were even moderately independent. Civilization, like all 
other kinds of development, has grown up partly through the 
greater efficiency proceeding from our specialization, through 
a division of labor among us. Our social system might thus 
be regarded as an organism itself, of which we are the units, 
while our cells, if they could think, might prefer to regard 
themselves as individuals in a society. 

There are, to be sure, differences between the relation oi 
our cells to us and our relation to human society, but are 
they as fundamental as we might at first suppose? Freedom 
of movement is one obvious difference. Yet cells are by no 
means always fixed in place. During development they move 
about a great deal, and even in maturity there are some that 
still do. The white blood cells rove over our entire body, 
through blood vessels and out of them, into the spaces be- 
tween the cells, wherever their own nature and the stimuli 
to which they respond direct them. 

Are we more free to follow our fancies? At least most of 
us know the force of economic limitations that tie us to our 
spheres of labor. While we exercise more or less choice in 
picking a vocation, we certainly are limited in this, too, by 
our innate ability, by our training, and by the availability of 
jobs, among other things. The distinction of free will be- 
comes very tenuous as we examine it. Nor must we blindly 
conclude that all social groups resemble our own human 
societies. Ants and bees are social no less than ourselves, yet 
they are governed almost as completely in their behavior 
by their instincts (that is, ultimately, by their genes) as white 
blood cells are. 

In our society, we, the members, are born and die, and 
others take our places while our social group lives on. So, 


too, within our bodies, cells are formed, live, and perish, 
their places then to be filled by others, their work to be 
taken over, or, occasionally, to prove an irreparable loss. 
Human societies, too, have ended and will end quite as we 
die, or as an ant hill is wiped out by deluge or famine. From 
such parallels as these, the biologist is led to see that, just as 
each man and woman may be studied as a society of cells, 
so a social group may be considered as a higher organism. 
This is not the whole truth, to be sure. On each level of 
organization, new and as yet unpredictable qualities emerge. 
Nevertheless, just as a man's life activities are clarified and 
rendered intelligible through our knowledge of the cell, so 
too our understanding of the social "organism" should be 
based on our scientific study of lower hierarchies of organi- 
zation. The biologist who knows his own dependence upon 
physics, chemistry, and mathematics is eager for a history 
that will portray man as at once the evolving creature and 
maker of his biological environment, 1 and for a view of our 
social problems that will take into account the biological 
laws of the organism. 

An organism may be regarded as an organism because its 
units labor in harmony for the common good. The cells in 
our bodies carry a common genetic pattern which underlies 
the harmony of their behavior, to this end. The social organ- 
ism has no genes and no mitosis. It must rely instead upon 
its culture pattern, acting in a thousand formative ways upon 
each newcomer to the group. In this realm at least, the trans- 
mission of acquired characteristics is a fact. We may, indeed, 
be thankful that it is, for it renders our culture pattern adapt- 
able-far more susceptible to change than man's genetic pat- 
tern, which is essentially the same today as a hundred thou- 
sand years ago. But is the culture pattern strong enough to 

iFor an excellent development of this point of view by a historian, see 
Progress and Power, by Carl T. Becker, of Cornell University (Stanford 
University Press, 1936). 


hold us, through education and tradition, to the required 
degree? Or is it in irresoluble conflict with our individual 
tendencies toward self-willed freedom and independence? 

These are questions we cannot answer today. We can only 
say with Donald Culross Peattie that "biologically considered, 
man is the sole being who has its destiny in its hands. And 
few of his species feel any sense of social responsibility higher 
than the fundamental one of begetting children. Yet now 
and then, as the years pass, comes a Noguchi, Pasteur, 
Beethoven, Lincoln, Asoka, Marcus Aurelius, or Plato [or, 
we might add, a Christ]. They are humanity as it might be." 2 


The hollow ball or blastula is growing. Were we to watch 
the process in a simple egg containing relatively little yolk, 
we would soon see that this growth is uneven. The cells 
around the animal pole become more and more active, grow 
faster and faster. Those at the vegetal pole lag far behind and 
do not divide nearly so frequently. The ball consequently 
becomes more and more lopsided (see Fig. 66). As the cells 
from the animal pole expand, the cells from the vegetal pole 
become tucked up into the interior. These movements are 
kept up until the embryo is first cuplike and then, as the lips 
draw together, like a sack. (Such a process is called invagina- 
tion, which means "pushing in to make a pocket.") The for- 
mation of the sacklike embryo, or gastrula, as it is called, is 
essentially the same in eggs which have yolk, except that the 
yolk is in the way of the formation of the pocket. In a frog's 
egg, which contains a moderate amount of yolk, the invagina- 
tion takes place to one side of the yolk-filled cells of the vegetal 
pole; while in eggs with an enormous mass of yolk, such as 
a bird's, cleavage has been quite ineffective except in a little 
cap of cells at the animal pole, and the invagination takes 

2 Peattie, D. C. An Almanac for Moderns, p. 312. G. P. Putnam's Sons, 
New York, 1935. 



Fig. 66. Four stages of the invagination that transforms the hollow blastula 
into a sacklike gastrula, as seen in many animals. The embryos are repre- 
sented as cut halves to show their interiors. Animal poles are at the bottom, 
vegetal at the top. (From Goldschmidt's Ascaris. Courtesy of Prentice-Hall, 

place at one side of this. In any event, the result is the same: 
Two layers of cells are produced, an inner and an outer; and 
the embryo has acquired a cavity open to the exterior, as 
shown in Fig. 66. 

The outer layer, which we call the ectoderm, being ex- 
posed to the external environment, comprises those cells 
which become specialized to respond to various sorts of ex- 
ternal stimulation and to coordinate the behavior of the 
organism. In other words, this means (1) the outer layer of 
the skin; (2) its products, such as our hair, nails, the enamel 
of our teeth, sweat, oil, and milk glands, and, in other ani- 
mals, feathers and parts of scales; (3) major parts of the sense 
organs; and (4) the entire nervous system. 

The inner layer, or endoderm, lines the new cavity with 
the opening to the exterior. This space is to become the 
digestive cavity. The endoderm consequently forms mainly 


the inner layer of the digestive system, with cells specializing 
in secreting mucus or various digestive enzymes, or in ab- 
sorbing the digested food. However, we shall see later that 
quite a number of other important organs grow from it as 
pouches or pockets. In birds' eggs, the endoderm, with the 
ectoderm on top of it, at first lies like a disk on top of the 
great ball of yolk. Gradually this disk will extend down over 
the surface of the yolk until finally it will completely enclose 
it, making what is known as the yolk sack. But this will take 
quite a while. In the meantime, the endoderm has already 
begun its work of digesting the yolk and transferring food 
to the overlying cells of the ectoderm. 

Now in human embryos, and, of course, in other mam- 
malian embryos likewise, there is very little stored yolk. 3 
Perhaps we should expect the human embryo to form first 
a blastula and then a gastrula, in the way a frog does, since 
the egg of the latter also has rather little yolk. However, 
this is not the course of our development. On the contrary, 
we develop in a manner reminiscent of a chick or lizard, 
and not like a frog— quite as though we carried a lot of yolk, 
or had once, and had never broken ourselves of still develop- 
ing in the immemorial way. 

After we have reached the berry-like stage, it can be seen 
that we have a distinct outer layer of cells. This grows faster 
than the inner mass, opening up a cavity between them, the 
inner mass remaining attached to the outer layer at the 
animal pole (Fig. 67^). This stage is comparable to the blas- 
tula of a reptile or bird with its yolk removed. 

Meanwhile, after a week or less of development, we have 
moved slowly down our mother's Fallopian tube, at the 
upper end of which we originated as zygotes by fertilization, 
and have now reached her uterus (womb). Here, at about 

3 One might note here another instance of what is apparently foresight. 
The human embryo has need for only a little yolk, as it will shortly be sup- 
plied with food through a connection with its mother's body. The amount 
it stores as an egg is correlated with what it will need later. 



^^5^ . 




Fig. 67. Sections through 
three stages in the early 
development o£ the rhesus 
monkey (Macacus rhesus), 
photomicrographs, magnifi- 
cation about 150 diameters. 
A, at nine days. A hollow 
sphere (blastocyst) with an 
inner cell mass at one pole; 
not yet implanted in the 
uterus. B, at ten days. Im- 
plantation has occurred, and 
the outer sphere has par- 
tially collapsed. The inner 
cell mass of ectoderm has 
become hollow, forming the 
amniotic cavity (Ac). Be- 
neath the ectoderm appears 
the first thin sheet of endo- 
dermal cells. C, at thirteen 
days, showing only the im- 
mediate vicinity of the em- 
bryo proper. At Ac, the 
amniotic cavity; at Ys, the 
empty yolk sack; between 
them, the embryonic disk of 
the embryo, made up o£ a 
layer of ectoderm (above) 
and a layer of endoderm (be- 
neath). Be, the cavity oE the 
blastocyst; Ut, tissues o£ the 
uterine mucosa; Bl, blood 
lakes containing blood cells. 
(From Streeter and Heuser. 
Courtesy of Carnegie Insti- 
tution of Washington) 

31 Ut Ac 

ys 31 Ut 


our tenth day of existence, we become firmly implanted in 
the surface layer of the uterus, which has meanwhile grown 
a great deal thicker, and has acquired an extraordinarily rich 
blood supply. Finally we burrow into and are quite covered 
over by the growth of this surface layer of the uterus, the 
uterine mucosa. The, inner cell mass lies buried deepest. 
Our bodies will form from this inner cell mass alone, and not 
from the outer sphere of cells, which serves another function. 
From the latter there shortly grow out little rootlike projec- 
tions of cells, which imbed themselves deep in the mother's 
tissues. Meanwhile quite a large space has opened up in the 
uterine mucosa about us, a space connected with our mother's 
blood vessels and filled with nourishing blood. Very early we 
are thus bathed in a lake of blood, from which oxygen and 
dissolved foodstuffs (sugar, amino acids, and so forth) can 
diffuse into our own fluid-filled central cavity and body cells, 
while our wastes (carbon dioxide, urea, and so forth) will dif- 
fuse in the reverse direction, into our mother's blood. 

At the time when we are becoming implanted in the mater- 
nal tissues, the inner mass of cells also becomes hollowed out, 
its tiny cavity surrounded by a layer of thin cells above and 
one of tall columnar cells below (Fig. 6jB). The latter flatten 
out into a thick plate of cells, the embryonic disk from which 
our body proper will develop. The rest of the inner cell mass 
and hollow ball at this stage will go to make up the auxiliary 
structures needed for our nourishment, respiration, and waste 
disposal during the long months we spend within our mother's 
body. At about the time of implantation a thin layer, the 
endoderm, makes its appearance, also splitting off from the 
inner cell mass. It too grows thicker, platelike, and proceeds 
to separate into a thick upper layer next to the ectoderm, and 
a thin sheetlike lower layer which surrounds the imaginary 
yolk (Fig. 67 C). At this stage of our development we corre- 
spond to the gastrula of a reptile or bird. 



An animal which develops only to the level 
of the two-layered sack 

Two great subdivisions, or phyla, of the animal kingdom 
comprise individuals who remain as adults at the develop- 
mental stage of the gastrula. One of these is the phylum of 
the sponges; but since they very peculiarly turn themselves 
completely inside out during their development, they can 




Fig. 68. The Hydra, a simple, fresh-water animal built on the plan o£ the 
two-layered sack. (Redrawn with modifications from Buchanan's Elements of 
Biology. Courtesy of Harper & Brothers) 

hardly serve as a typical example. A better one is provided 
by the phylum of the coelenterates, which includes jellyfishes, 
sea anemones, corals, and, among others, the relatively sim- 
ple fresh-water polyp, Hydra (Fig. 68). 

The Hydra is, indeed, except for the crowning fringe of 
tentacles around the mouth, remarkably like a gastrula. 4 

4 The Hydra, it is true, does not attain its gastrula-like organization by 
invagination. The endoderrn is formed from the ectoderm of the blastula by 
an inward movement of cells from the surface, thus providing a deeper layer 
beneath the ectoderm. Later, at the vegetal pole, an opening is formed. 


These tentacles, too, are simply projections of the sack-like 
body. It is not in the general organization of the body that 
the Hydra surpasses the gastrula, but in the degree of speciali- 
zation which the cells attain. Let us see just how effective a 
division of labor is possible among the cells when the body 
plan is simply that of two layers enclosing a cavity open at 
one end to the exterior. 

The gastro vascular cavity, as it is called, is a very useful 
thing. Since it has an opening to the outside, food can be 
taken into it and partially digested there, relieving each cell 
of the necessity of entirely digesting its own food internally. 
Since every cell, too, has a surface exposed either to the outer 
fluid environment or to the inner, excretion and respiration 
are simple matters requiring no specialization beyond the 
mechanisms of the single cell. With these handled directly, 
and with currents in the central cavity supplying food to all 
parts, there is no need for special means of distribution. Spe- 
cialization is correspondingly limited to the activities of nutri- 
tion, sensation, coordination, response, protection, and re- 

The provision of two layers, to begin with, enables the 
outer layer, in contact with the environment, to specialize 
in the functions of protection and food-getting, while the 
inner layer, exposed to the internal cavity, specializes in the 
various digestive functions. Besides this, both layers have 
certain kinds of specialized cells, adapted for sensation or 
coordination, or for movement. 

In addition to all these, each layer has unspecialized cells 
from which the specialized cells develop. Such a cell in the 
ectoderm may differentiate into a sensory cell, or into a nerve 
cell, or into a stinging cell, or into a cell which is protective 

Some biologists believe this is the more primitive mode of gastrula formation, 
and that invagination evolved later, as a developmental short cut. Be that 
as it may, the Hydra is clearly a two-layered sack when mature, and affords 
an excellent example of specialization on this level of organization. 


at its outer end and contractile like a muscle cell at its inner 
end. A similar cell in the endoderm may differentiate into 
a gland cell which secretes slimy mucus and digestive en- 
zymes; or into sensory or nerve cells; or into cells muscle-like 
at their bases and, at the other end, producing flagella that 
lash the food about in the central cavity, as well as pseudo- 
pods that engulf food, as does an ameba, for internal diges- 

Coordinated behavior arises from the fact that the nerve 
cells communicate with their neighbors by means of the 
branches which each extends out from its cell body. Thus 
over the whole organism there is a network of nerve cells, in 
contact with one another as well as with the sensory cells on 
the one hand and the muscle cells on the other. Yet there is 
nothing recognizable as a brain, nor even any provision for 
centralized control over behavior. Only around the mouth 
nerve cells are especially abundant. 

Hydra reproduces both sexually and asexually. Sex organs 
are formed from the undifferentiated cells of the ectoderm 
at certain seasons of the year, and the same polyp may pro- 
duce both eggs and sperms. The rest of the year the polyp 
simply puts out buds from its body. The unspecialized cells 
in a bud proceed to generate a new Hydra, mouth, tentacles, 
and all, its cavity at first communicating with that of the par- 
ent. Eventually the cavity is closed off, the tissues are pinched 
away from the parent's, and the offspring becomes inde- 

The two-layered sack stage of development is evidently 
capable of considerable differentiation. Yet the radial sym- 
metry, implying lack of a head and the absence of central 
nervous control, and the lack of any provision for internal 
transport have limited the behavior and the size of those ani- 
mals which have retained this general plan of organization. 
Locomotion is slow and laborious, adaptability is slight, and 
life at all is possible only in an aqueous environment. 



In our own development, we may recall, the gastrula stage 
is greatly modified. Nevertheless, there is a tiny canal through 
the ectoderm providing an opening from the digestive cavity. 
Stretching in one direction from this opening there forms 
a shallow groove in a narrow thickened band where ectoderm 
and endoderm meet and merge into undifferentiated tissue. 
This is the primitive streak. In the opposite direction runs 
another shallow groove in a thickened band of cells, which is 
the beginning of our central nervous system, forming just as 
it does in the frog. 

If we were to watch a frog or salamander embryo devel- 
oping within its transparent coat of jelly, we would see a 
great external change appearing not long after the gastrula 
was complete. At the lip of the opening into the central 
cavity a shallow groove appears, running forward toward 
what in the future will develop into the head. It lengthens 
and deepens; folds margin it, grow higher, curl over toward 
one another. At the head end, the trough is considerably 
broader. Behind this region the folds meet first; then, gradu- 
ally, they fuse all the way in both directions (see Fig. 75). 
When done, this process has produced a tube extending along 
the back and ending in a bulb at the head. Thus, there origi- 
nate from the ectoderm the spinal cord and brain, making up 
the central nervous system. 

These two grooves, the primitive streak and the neural 
groove, between them mark out the primary axis of the body, 
from head to tail. In Chapter IV (pp. 192 £.), the formation of 
the organizer of the neural tube in the cells located at the 
dorsal lip of the pore of the gastrula was described. The 
primitive streak in the embryo of a mammal or bird is 
similarly located in relation to the neural tube, and experi- 
ments have shown that it produces the organizer of the neural 


tube. It is therefore generally regarded as a structure homolo- 
gous to the dorsal lip of the pore of the gastrula, although 
superficially it looks very different. 

Another important thing about the primitive streak is that 
from it on either side there begins to arise a third layer of cells 
(Fig. 69). This lies between the ectoderm and the endoderm. 
It is the mesoderm, which provides most of the bulk of our 
body, for from it come muscles and bone, cartilage and 

Ectoderm Primitive Mesoderm 

Endoderm Primitive Streak 

Proliferating Mesoderm 

Fig. 69. A transverse slice across a human embryo, showing how the meso- 
derm grows from the primitive streak. Note that the cells in the three layers 
are already different in character. Magnified about 150 diameters. (From 
Arey's Developmental Anatomy, after Streeter. Courtesy of W. B. Saunders 

connective tissues, heart, blood vessels and blood, kidneys, 
reproductive organs, and the deeper layer of our skin. 

An animal which gets no farther in general 
development than mesoderm formation 

Under stones in our streams and ponds there may often 
be found numbers of small flatworms (Fig. 70), each gliding 
smoothly over the rock like a snail. Unlike Hydra and its 
relatives, this creature obviously has a head, with a couple 
of projecting lobes on the sides and two eyes, appearing rather 
crossed, between them. 

A line drawn from the tip of the snout to the tip of the 
tail would divide this animal into two halves, each side a 
mirror-image of the other. In other words, the flatworm is 
bilaterally symmetrical. As a consequence, it has a front end, 
a "head," and the sensory organs tend to be concentrated 






Globules of 


Fig. 70. A, Planaria, a flatworm. B. one of the flatworm's excretory, or 
"flame," cells. (Redrawn with modifications horn diver's Animal Biology, 
ed. 2. Courtesy of Harper ^ Brothers) 

here where the animal can be informed most promptly of 
its approach toward food or danger as it moves forward. 

Examining its internal organization, we notice that it has 
a well-developed intermediate layer between the ectoderm 
and endoderm. The cells of this mesoderm are differentiated, 
in the first place, into muscle cells, which enable the animal 
to contract, change its shape, or turn to right or left. (Its 
smooth, gliding motion, however, comes from cilia growing 
on the under surface, which beat in a film of mucus pro- 
duced by gland cells, also on the under surface. Like a cater- 


pillar tractor, the flatworm thus supplies its own roadway.) 
Some of the muscles encircle a portion of the digestive cavity 
near the mouth, thus forming a pharynx, useful for sucking 
in the food. 

Other cells in the mesoderm specialize for excretion; for 
where there is mesoderm, there are cells away from the sur- 
face of the body, for the disposal of whose wastes special pro- 
vision must be made. These special excretory cells lie at the 
ends of a branching system of tubes which communicates 
with the external surface of the worm. Each one of these 
cells has a big tuft of cilia nickering like a flame in the duct, 
and thus producing currents that sweep the wastes down the 
ducts and out of the body. (For this reason they are called 
"flame cells.") Opposite the "flame," each excretory cell 
has numerous branches which project among the other cells 
of the mesoderm and into the spaces between them, and 
there collect the wastes. 

Most of the mesoderm cells, however, are unspecialized. 
They assist in the distribution of materials, and at least many 
of them can at need turn into the various kinds of specialized 
cells. Because of this, if we cut a flatworm into bits, each 
part will be able to regenerate what it lacks, and can develop 
into a perfect individual. 

There is also considerably more advanced specialization 
in ectoderm and endoderm than in Hydra. There are vari- 
ous kinds of sensory cells, taste is present, and the simple 
eyes we have already mentioned provide a response to light, 
although they cannot form an image. The nerve cells are 
organized into two long chains, with cross-connections like 
the rungs of a ladder; and between the eyes there are large 
masses of nerve cells. These ganglia, as they are called, fore- 
cast by their position the brain of higher animals. 

The digestive cavity is a sack lined with endoderm, as in 
Hydra. Sometimes the mouth is at the snout. More fre- 
quently it is in the middle of the underside (see proboscis). 
and the digestive cavity branches to all parts of the body, as- 


sisting in the growing problem of internal distribution of 

Reproductive organs of both sexes develop in each flat- 
worm, as in the polyps. They are really the most specialized 
of all the systems. There are numerous testes, which produce 
sperms, at the ends of a branching system of ducts that leads 
to the penis and genital pore. There is also a pair of ovaries, 
which produce eggs, at the ends of long ducts into which open 
numerous yolk and shell glands; and there is a pouch into 
which the penis of another worm enters for the transfer of 
sperms. It is worth noticing that even hermaphroditic ani- 
mals like the flatworm rarely fertilize their own eggs. Just 
as with us, inbreeding would result in the homozygous condi- 
tion of any recessive genes, and most of these, as we know 
from many organisms, if not from the flatworm, are harmful. 

To sum up, a flatworm is far closer to our type of organi- 
zation than a polyp is. Its main advances are: (1) bilateral 
symmetry, including an emergent head; (2) mesoderm, in- 
cluding specialized excretory and muscle cells; (3) a cordlike 
nervous system running the length of the body, with an indi- 
cation of a brain. Life on this level of development has al- 
ready become surprisingly complex. 




We have seen how, as embryos, we became imbedded 
in the lining, or mucosa, of our mother's uterus, and how 
our outer layer of cells proceeded to send out rootlike growths 
into the maternal tissues. This thin outer layer is soon 
strengthened by the addition of a layer of mesoderm. This in 
turn separates into two layers, an outer layer that lies against 
the ectoderm, and an inner layer that lies against the endo- 
derm. The large cavity between the outer layer and the 
embryo proper is eventually completely lined with meso- 


derm. In this fluid-filled cavity, the coelom, the embryo and 
its yolk sack dangle from the outer sphere by means of the 
body stalk (Fig. 71). 

The outer layer formed in this fashion by the fusion of 
ectoderm and mesoderm is the chorion. It not only serves to 
protect and anchor us, but acts as the primary organ which 





• Extra-embryonic- 



Fig. 71. Diagrammatic cross sections through early human embryos, together 
with their membranes. A, at approximately twelve days old. Amniotic cavity 
and yolk sack are present. B, at approximately fifteen days old. Villi are 
just beginning to grow out from the chorion. C, at approximately twenty 
days old. The villi are well developed all over the surface of the chorion. 
Tissues: ectoderm, black; endoderm, medium gray; mesoderm, pale gray. 

cares for our embryonic nourishment, respiration, and dis- 
posal of wastes, through exchange with the mother's blood to 
which it is exposed. Later a large part of the chorion con- 
tributes toward the formation of the placenta (see p. 252). 

Within the inner mass of ectoderm a small cavity also ap- 
pears, at the age of about ten days. This rapidly increases in 
size, and lengthens as the embryo does. The walls and roof 
thin out to a mere membrane, ectoderm on the inside, meso- 


derm outside, remaining attached only at the hind end to 
the chorion above. This membrane is the amnion, and its 
attachment to the, chorion is the body stalk, a forerunner 
of the umbilical cord which runs from our navel to the 
placenta. The cavity of the amnion fills up with a fluid, 
clear and watery, and this cradles our developing body, which 
forms the floor of the cavity. 

In reptiles and birds the amnion and chorion arise as a 
fold of the body wall extending all around the embryo, and 
then growing up and over until it meets on top of the embryo 
and encloses it. In our development the same end is attained 
by the appearance and enlargement of one cavity in the 
inner mass of ectoderm, and of another in the mesoderm. 
Here is an example where our development has effected a 
short cut and become more straightforward when compared 
with egg-laying animals. 

Next to the chorion is the great cavity (or coelom), com- 
pletely lined by mesoderm. In the lower animals, as in round- 
worms 5 or segmented worms, for instance, such a cavity is of 
great value. In roundworms, which have no circulatory system, 
the coelom provides an easy channel for the distribution of 
dissolved foodstuffs and gases (oxygen and carbon dioxide). 
In both roundworms and segmented worms it serves in the 
collection and disposal of wastes. For us, as for the other 
higher vertebrates, most of this cavity lies outside the embryo 
proper and is gradually eliminated by the enlargement of the 
amnion. As for the part that is left within the body after the 
side walls of the body grow down and enclose the gut, what 
with our elaborate circulation and our highly efficient 
lungs and kidneys, there is little more function left for it 
than to provide a space where such organs as lungs, heart, 
and stomach may expand and contract. 

The endoderm, now covered with a layer of mesoderm 

5 The zoologist may object that the body cavity in roundworms is not 
a true coelom. It has no inner layer of mesoderm. Functionally, however, 
it plays the same role. For a popular study of biology based on the round- 
worm see Ascaris, by Richard Goldschmidt (Prentice-Hall, New York, 1937). 


which will later provide muscles for moving food through 
the digestive tube, lengthens out into a hollow gut, quite 
empty. Strangely enough, the lower part of this gut continues 
to grow out as a sack enclosing an imaginary mass of yolk, 
and, at the age of three and one-half weeks, is approximately 
as lame as the whole body of the embryo (Fig. 72). 




Upper Ja to 
Lower Jaw 
yolk Sack 


Fig. 72. Human embryo about three and one-half weeks old. (Redrawn with 
modifications from Arey's Developmental Anatomy, after His. Courtesy of 
W. B. Saunders Company) 

After reaching a maximum size at six weeks, the yolk sack 
stops growing and becomes smaller and smaller in proportion 
to the rest of the body. Finally it is gathered into the umbili- 
cal cord, the scar of which is the navel. Could any better 
example of the uselessness of certain features of our develop- 
ment be offered? Why do we continue to produce a structure 
whose value we can explain only in terms of its usefulness to 
animals which develop from eggs containing a lot of yolk- 
fishes, frogs, reptiles, and birds? Why have we genes, to put 


it in other terms, which regulate our development along lines 
suitable not to our condition but to that of more primitive 
forms? Why, if not that along with our characteristically 
"human" genes we have others we might better call "fish" or 
"reptile" genes? 

This is not an isolated example. The very next structure 
to be discussed presents similar features, and we shall run 
into many more examples of a lack of straightforward devel- 
opment. Before we are so much as three weeks old, another 
sack begins to protrude from our gut behind the yolk sack, 
and to grow up into the body stalk. This is the allantois. 
Two large arteries and a big vein accompany it and grow 
on into the chorion. Here the blood coursing through the 
arteries is distributed into branches running down into the 
rootlike projections of the chorion, and thence into a myriad 
of exceedingly tiny, microscopic vessels with very thin walls, 
called capillaries. From these it is gathered into branches 
of the big vein, and so goes back toward the heart. While 
these blood vessels play an important part in carrying on 
the necessary exchange of food, oxygen, and wastes between 
us and our mother's blood, the allantois itself gradually 
dwindles away. 

When we are between six and seven weeks old the cloaca, 
that part of the gut behind the junction of the intestine and 
allantois, undergoes a startling change. The wedge of tissue 
in the anterior angle of the junction commences to push 
rearward all the way to the body surface, until the cloaca 
is split into two portions that will later open to the exterior 
separately. Ducts from the kidneys and reproductive organs 
grow down and open into the part connected with the allan- 
tois, and after birth this modified portion of the cloaca func- 
tions as our urinary bladder. 

This roundabout way of developing a bladder seems quite 
inexplicable until we turn for enlightenment to the birds 
and reptiles. Animals which develop on land within eggs 
require, just as much as the rest of us, some means of breath- 


ing and disposing of wastes before they hatch. How does a 
chick breathe when inside an egg? We know enough already 
to realize that a large surface will need to be exposed, if the 
exchange of gases is to be adequate. How is this provided? 
The answer is— the allantois. This bladder, with its great 
blood vessels, grows until it fills all the space between the 
amnion and chorion. It fuses with the latter and, thus, comes 
to lie just under the shell, exposing the blood to the air over 
as large an area as possible. Moreover, the protein wastes 
of the body can be deposited in the allantois where they will 
do no harm to the developing embryo. Later, quite as in our 
development, the cloaca is partitioned and the allantoic part 
serves in adulthood as the urinary bladder. But in the primi- 
tive fishes and the amphibia the cloaca is never divided. The 
urine, the reproductive cells, and the waste fecal matter min- 
gle there, and are voided through a common opening. 

Here again we have run into a phase of our development 
which we can interpret only in terms of usefulness to more 
primitive forms of life. It is as though we had started our 
development under the delusion that we were to pass through 
it like a chick, and then suddenly came to a realization 
that instead we were sheltered within our mother's womb, 
and had to readapt ourselves as efficiently as possible to new 
modes of securing food and oxygen and of disposing of 
wastes. This, of course, cannot be so. There is no conscious, 
but rather a purely automatic, control over development. 
Then why does our genetic pattern shape our development 
along lines useless and inefficient to us, though of value to 
more primitive animals? It can only be, as pointed out in the 
introduction to this chapter, that our present genetic pattern 
is a modification of a less advanced ancestral pattern that was 
adapted to different conditions. In spite of all its marvelous 
adaptation to life and growth within the uterus, our develop- 
ment manifestly shows that these features are but super- 
imposed on the ancient status of the yolk-crammed egg laid 
and then left to its own resources. 



The amnion later swells tremendously, filling all the avail- 
able space between our chorion and our body. Around the 
body stalk and yolk sack it forms a sheath, binding them to- 
gether into the umbilical cord (Fig. 73). Meanwhile the outer 
half of the chorion has become quite bald, the rootlike growths 
continuing to develop only where, as we grow, they still 


-Amniotic Fluid- 


-Allan tois 


Actual lengths of embryos 



yolk Sack 

Fig. 73. Diagrams of human embryos with their membranes, to show how the 
enlargement of the amnion presses the yolk sack and body stalk together to 
form the umbilical cord. A, at about four weeks of age. B, at about six 
weeks of age. 

remain in contact with the lining of the uterus. This area 
of contact is finally reduced to a platter-like structure made 
up of the branching growths from the chorion, the surround- 
ing lakes of maternal blood, and the underlying tissues of 
the uterus, with their abundant blood supply. This struc- 
ture, made partly from the embryo, partly from the mother, 
is the placenta, chief organ of our embryonic life. 



Third week 

We have run somewhat ahead of our story in taking up the 
final development of the embryonic membranes-now to go 
back and notice a few things that have been happening in 
the meantime. 

When we are about two and a half weeks old, the floor of 
the cavity roofed by the amnion is still quite disk-shaped. It 
is from this disk that our body will form. But growth is pro- 
ceeding rapidly only at one end of it, so that the disk soon 
becomes pointed and elongated. The primitive streak ap- 
pears in this region of rapid growth, with the pore into the 
gut at its anterior end. The amnion meanwhile has separated 
from the chorion everywhere along the top except at the 
posterior end of the embryonic disk, so that the body stalk is 
here. In just a day or two our length doubles, while there 
is no increase in width (Fig. 74). 

Next, the region in front of the pore begins to grow more 
rapidly than the hinder part, and the relative positions of 
the pore and the primitive streak are thus pushed farther 
and farther back. From the pore a shallow neural groove 
extends forward toward the head, and just under this groove 
a long rod of mesoderm grows forward from the front lip 
of the pore. At this time, too, we begin to get some thickness 
to our bodies. No longer so nearly like a plate spread on 
top of the yolk sack, the body stands out above it like a 
cylinder, slightly sway-backed in the middle. 

The side walls of the body roll in underneath and cut off 
a tubular portion of the gut cavity from the yolk sack, leav- 
ing them communicating only in the center. At front and 
rear the tips of this digestive tube lengthen until they touch 
the body surface, leaving only a thin membrane. These will 
eventually rupture to open up mouth and anus. 

The roundworm, which has been mentioned already in 



Cut Edge of 








__ Body 


(Length Of} mm.) 


(Length L5 mm.) 

Fig. 74. Early human embryos seen from above. A, about seventeen days old 
(Streeter). B, about twenty days old (Spee). (Redrawn with modifications 
from Arey's Developmental Anatomy. Courtesy of W. B. Saunders Company) 

connection with the body cavity (see p. 248), is a fair repre- 
sentative of an animal which stops on this general level of 
development. It has a digestive tube, running all through 
the body from mouth to anus, and a body cavity, with 
mesoderm lining one side (the outer). The nervous system, 
however, forms on the underside, and is not a hollow tube; 
nor is there any sign of a rodlike structure down the back. 
These last two are features found only in animals much 
closer to us in the scale. Yet we should not imagine that 
roundworms are altogether simple and primitive creatures. 
They are often specialized in amazingly individual ways for 
the life of a parasite, and they are the first examples we meet 
whose individuals are wholly male or female. Even the much 
more complex segmented worms are hermaphroditic. 


Fourth week 

During the fourth week of our lives important develop- 
ments come thick and fast. 

(1) The neural groove running forward from the pore 
deepens, folds grow up along it and arch over toward one 
another, finally fusing to make a tube, the rudiment of the 
spinal cord. In front the tube broadens out into three suc- 
cessive bulges, which take longer to close. These vesicles are 
the three original parts of the brain: forebrain, midbrain, and 

(2) Underneath the neural tube, the rod of mesoderm 
growing forward from the pore is now complete. It is the 
forerunner of the backbone, and runs from the tail well up 
into the head. Tough, though not bony-for bone first de- 
velops a good deal later-this notochord, as it is called, is the 
first skeletal structure to appear. 

(3) Mesoderm lying to the sides of the notochord begins 
to be divided into blocklike segments, arranged in pairs to 
right and left. These first show up just back of the hind- 
brain; and, as the neural tube progressively closes over in 
the direction of the tail, the paired segments keep pace with 
it. By the end of the week the entire thirty-eight pairs have 
appeared (Fig. 75). 

(4) Blood vessels, blood, and a heart begin to develop from 

the mesoderm. 

(5) In the head and neck region small tubes grow in the 
mesoderm, a pair to every pair of segments. At one end each 
tube opens into the body cavity; at the other, it turns toward 
the rear and grows until it meets the tube in the next seg- 
ment, thus forming a duct which soon connects all the tubes 
on one side of the body (see Fig. 84, p. 283). These are ex- 
cretory tubules. The two ducts grow back until they empty 
into the cloaca. 

Earthworms and their marine relatives halt at a similar 
stage of the developmental journey. They are obviously seg- 



Fig. 75. Body form in early human embryos. A, the primitive streak stage, 
nineteen days old (magnified about 32 diameters). B, with 3 mesodermal seg- 
ments and a deep neural groove, early in the fourth week (magnified about 
30 diameters). C, with 7 segments; neural tube closing (magnified about 25 
diameters). D, with 10 segments; brain vesicles closing (magnified about 
25 diameters). E, with 19 segments, twenty-five days old, with a well-folded 
cylindrical body (magnified about 16 diameters). All but E are in dorsal 
(surface) views; E is seen from the side. (From Arey's Developmental Anat- 
omy, after Streeter. Courtesy of W. B. Saunders Company) 

merited, and they have a well-developed circulatory system, 
with blood, arteries, veins, and even pulsating vessels that do 
the work of a heart. They also have a pair of excretory tu- 
bules in each segment. These open into the body cavity at 
one end, like ours; at the other, however, while they pass to 
the rear, they open separately through the body wall instead 
of forming two continuous ducts, each opening to the outside 
at one point only. 

Earthworms, however, like roundworms, have their nerv- 
ous system running down the ventral (belly) side instead of 
down the dorsal (back), like ours; and they have no trace of 
a notochord. A notochord and a dorsal neural tube make 
their appearance only in the lowest members, of the great 
phylum of the chordates, to which we belong. These primi- 
tive chorda te relatives of ours are queer enough, to be sure, 
and one of them is distinctly like a worm in outward ap- 


If we continued to examine our embryonic development 
in this fashion, week by week, we would see again and again 
that various groups of animals which have been developing 
as we do halt or pursue side lanes of specialization. In the 
little lancelet (Amphioxus), which looks like a fish without 
jaws or paired fins, ears, or eyes, and has neither bones nor 
cartilages, there are not only a notochord and a dorsal neural 
tube out also several dozen gill slits, opening in pairs from 
the pharynx to the outside. This is a feature which we de- 
velop in our fourth week, although the pouches in our throat 
and the grooves which form in the skin above them are 
separated by a thin membrane which is usually never rup- 
tured. Nor have we as many gill slits as the lancelet— only 
four furrows on each side are visible externally, and inside 
only five pairs of pouches can be counted (Fig. 76). 

Later in this same week our eyes and internal ears appear, 
lateral projections on the head grow together to form jaws, 
two pairs of limb buds pop out, and, within the body, carti- 
lage (gristle) begins to form from parts of the mesoderm. 
Here we part company with the sharks and rays. In our 
eighth week bone begins to form around the notochord 
in blocks— fishes share a backbone with us, but develop a 
swim-bladder and fins as we go on to develop lungs and limbs. 
The amphibians— frogs, toads, newts, and salamanders— are 
kept close to water because their eggs must develop in it. 
They are not provided with an amnion to protect them or an 
allantois for respiration and excretion before hatching from 
the egg. Only reptiles, birds, and other mammals accompany 
us here. Finally, only mammals form a placenta for the pro- 
longed nourishment of the embryo within the mother's 
uterus, grow hair, and produce mammary glands for suckling 
the young. 

Step by step we pass the stages where we become readily- 
distinguishable from fish, from frogs, from reptiles and birds, 
from other mammals, and finally from the monkeys and 





A —4.2mm. 

3 ^— 7.5mm. 

C 16./ mm. 

J) — — — 23.omm. 


Fig. 76. Four stages in the development of form in the human embryo. A, 
about four weeks old (4.2 mm.). B, about five weeks old (7.5 mm.). C, about 
seven weeks old (18.1 mm.). D, about two months old (23 mm.). The bars 
indicate the actual crown-to-rump lengths of the embryos. (Redrawn: A, 
with modifications from Arey's Developmental Anatomy, after His. Courtesy 
of W. B. Saunders Co. B, with modifications from Marshall's Vertebrate 
Embryology, after His. Courtesy of G. P. Putnam's Sons. C, from Minot's 
A Laboratory Text-Book of Embryology, ed. 2. Courtesy of The Blakiston 
Co. D, from Bailey and Miller's Text-Book of Embryology, ed. 5, after His. 
Courtesy of William Wood & Co.) 


apes. When two months old, we are recognizably human, 
although our proportions are anything but what they are 
later. The furrows in the neck have disappeared, and the 
tail, so prominent at six weeks, is about gone. Our head 
is still as large as the rest of our body, with very weak 
chin, flat nose, and eyes far apart. But it is definitely a face 
and not a monstrous caricature. There are tiny fingers and 
toes on the limbs, and before the end of another month 
sex can be readily distinguished. Muscles, too, begin to 
twitch and gain strength through exercise at this time. 

From now on the outward changes are mostly in propor- 
tion, because of altering rates of growth in different parts 
of the body. There is, of course, an enormous increase in 
size and weight, for at the eighth week we weigh only one 
gram (1/28 oz.) and from crown to heels measure slightly 
more than an inch, while at birth we are on the average 3,300 
times as heavy and seventeen times as long. Yet, as a matter 
of fact, we actually grow more and more slowly, for while we 
still have most of our weight to put on, it is steadily less in 
comparison with the total. During the first month of our 
growth we increase our weight about 40,000 times; during 
the last month before birth, we increase it by only a little 
over one third! 


Up to this point we have traced the major events in our 
development in a single sequence, but now the stage becomes 
overcrowded and it grows ever more difficult to keep all the 
threads of the plot in mind at once. It seems better to con- 
sider each great life problem separately, and to see how each 
in turn is met. 

The first system in our bodies to reach a functional level 
is neither the digestive nor the nervous system, even though 
these, as we have seen, are started much before any others. 


The reason for their tardiness lies in the special provision for 
nutrition, respiration, and excretion made for all mammalian 
embryos through the placenta. There is no significant need 
for a system to digest food that enters our bodies from our 
mother's blood already predigested. Nor is there need for a 
system to coordinate responses before any effective means 
of making responses has developed! There is, however, from 
very early in our growth a need for an effective carrier of 
dissolved foods, oxygen, and wastes. The first system to begin 
functioning as a whole is the circulatory system. 

Shortly after the mesoderm splits and forms a body cavity, 
blotches begin to show up in the mesodermal layer next to 
the endoderm, out on the yolk sack. These are groups of cells 
known as blood islands, for some of them differentiate into 
red blood cells, and others become flat and line spaces in the 
mesoderm that gradually fuse into primitive blood vessels. 

The blood 

The blood itself is composed principally of water contain- 
ing: (a) dissolved salts, in concentrations strikingly similar 
to those in sea water; (b) dissolved foodstuffs and wastes; (c) 
colloidal proteins, among them those responsible for the 
capacity of the blood to clot, and the resistances to various 
diseases, poisons, or the allergies to various foods or pollens; 
(d) the several types of white blood cells, helpful in com- 
bating bacterial invasions; and (e) the red blood cells, whose 
function is to convey oxygen to the body cells in union with 
hemoglobin. Hemoglobin contains iron, and its synthesis is 
the most important use of this element in the body. The 
blood cells are formed during development in a variety of 
places, first, as we have seen, in the blood islands of the yolk 
sack. A week later, they are produced in the unspecialized 
mesoderm of the body and in the blood vessels; the follow- 
ing week (the sixth) the factory shifts to the liver. Some 
weeks later the spleen, the thymus, and the lymph glands 
take over; and from the third month, with the development 


of the long bones, the red bone marrow within them be- 
comes the main source of the red blood cells, and after 
birth the only source of all types of blood cells. An inter- 
esting fact is that the first red blood cells are released into the 
blood stream while still large and nucleated, like those of 
fishes. These give place to a type with a smaller nucleus, like 
those of reptiles and birds, and only in the liver is there pro- 
duced for the first time the mammalian type, which loses its 
nucleus before it enters the circulation and thereafter cannot 
undergo mitosis. 

When and where the blood proteins are first produced is a 
matter of doubt. Later, the liver is their chief source; but 
some kinds come from the ameboid cells of the spleen, lymph 
tissues, red bone marrow, and the epithelium of sinuses and 
blood vessels. At all events, it is certain that, although the 
capacity to produce is present, actual production in many 
instances (immunities, allergies, and so forth) occurs only 
after exposure to the antigen, a foreign protein substance. 
The capacity of the blood to clot is also slow in developing. 
An infant's blood clots poorly until eight days after birth, 
and not with normal speed for about a year. This incapacity 
is sometimes fatal at birth, for the squeezing which the skull 
must undergo in passing through the pelvic ring of the mother 
often results in small brain hemorrhages, particularly in the 
prematurely born. An estimated one fourth of all birth in- 
juries are due to this. For some time it has been known that 
vitamin K, found most abundantly in spinach and alfalfa, but 
scarce even there, is necessary for the production of normal 
amounts of prothrombin, one of the substances requisite for 
clotting. Feeding the vitamin to an expectant mother or to 
the newborn infant is effective in speeding up the develop- 
ment of prothrombin, and so in bringing about normal clot- 
ting. We have here an excellent example of the way in which 
a normal rate of development is conditioned by the abun- 
dance of a necessary raw material in the environment. 



The blood vessels 

In the fourth week, the primitive vessels have developed 
into a symmetrically paired system, looping down over the 
yolk sack, then up into the head, and along the back toward 






Fig. 77. The human circulatory system at about three and one-half weeks. 
Arteries are shown black or stippled; veins are shown in outline or cross- 
hatched. (Redrawn with modifications from Arey's Developmental Anatomy, 
after Felix. Courtesy of W. B. Saunders Company) 

the tail, giving off the branches to the yolk sack and other de- 
veloping organs. Two of these branches are exceptionally large 
and follow the allantois into the body stalk. They are the 
umbilical arteries. Only one large vein comes back from the 
umbilical cord, but it forks as it enters the body and passes 
toward the head. Also by this time the two big blood vessels 
in our necks fuse; and this rudiment of a heart begins to pul- 
sate, at first feebly, then stronger and more rhythmically, 
pumping the fluid in the vessels forward to the head, then 
down the back and around to the heart again (Fig. 77). 

Blood vessels carrying blood away from the heart are called 
arteries. Those bringing blood back to the heart are called 
veins. (In Fig. 77 arteries are solid black or stippled and 
veins are in outline or crosshatched.) In the placenta and in 


all the organs blood is conveyed from arteries into veins 
through a network of myriads of microscopic blood vessels, 
the capillaries. These have such thin walls, no more than a 
single layer of very flat cells, that water and most dissolved 
substances can readily enter and leave the vessels. Thus the 
spaces between cells are filled with a fluid that is blood strained 
of its solids. From this fluid food and oxygen enter the cells 
by osmosis and wastes are received in return. 

The circulatory system is at this time a single circuit. All 
blood leaving the heart through the arteries is distributed to 
the body or placenta, passes through capillaries, is collected 
into veins, and returns to the heart. With each circuit some 
of the blood— that which goes to the placenta— is purified of 
wastes, and receives a fresh supply of food and oxygen. Part 
of this blood, after returning to the heart, is sent to the body, 
but part of it is returned to the placenta. And each time, too, 
some of the blood, filled with wastes, and needing replenish- 
ment of foods and oxygen, is, nevertheless, distributed again 
to the organs. This is certainly not very efficient, but still we 
manage to get along. 

The remainder of the development of our circulatory sys- 
tem is largely concerned with remodeling this one-circuit 
system into an efficient double circuit. All the blood from 
the body is pumped to the lungs for a fresh supply of oxygen, 
and all the blood from the lungs is pumped to the body. In 
this change the lungs take the place of the placenta in the 

In some respects the single-circuit system is more complex 
than that which takes its place. An early simplification is a 
fusion of the two big arteries along the back into a single 
one, the aorta, or trunk artery of the body. In front, how- 
ever, the double system persists. Through the fourth, fifth, 
sixth, and seventh weeks these paired loops, or arches, of the 
aorta go through an extraordinary transformation. They 
keep forming short cuts until there are five main pairs of 



arches, and even traces of a sixth. Meanwhile those in front, 
like oxbows in a river which have been robbed of their water 
by by-passes, dwindle away, either wholly or in part. 

to head-* 


to body 

from — \ 
heart Ik 

3 « 


heart lungs 




of heart 

Up to birth Afterbirth 


of heart 

Fig. 78. Diagrams illustrating the successive changes in the human arterial 
arches up to and after birth. 

As seen from below (a ventral view), the system alters suc- 
cessively as shown in Fig. 78. 

The first two pairs of aortic arches (1, 2) degenerate 

The dorsal connections between the third and fourth pairs 
of aortic arches (3, 4) degenerate, and thereafter the third 
pair supplies blood only to the head. 

The right arch of the fourth pair breaks away and supplies 
blood only to the right shoulder and arm. 


The left arch of the fourth pair becomes the trunk artery, 
the dorsal aorta. 

The final or pulmonary pair disjoins so as to supply only 
the lungs. 

A spiral partition grows up the aorta, so that the pulmonary 
arches get blood from the right side of the heart, and the 
other arches from the left side. 

This extensive revision may appear quite incomprehensible 
to us. Yet there is a reason why it occurs in this fashion. We 
may notice, for example, that the digestive tube produces a 
pouch between each of these pairs of arterial arches, and that 
a corresponding pocket forms in the outer skin. These keep 
deepening until they nearly meet— only rarely do they break 
through to become perforations of the throat. And we may 
notice that in the mesoderm alternating with these pouches 
and pockets supporting bars of cartilage develop. Now sup- 
pose we look at a fish. We see at once that what we have been 
looking at is the exact arrangement of a fish's gills. Except 
that in a fish the pouches and pockets open all the way 
through, so that water swallowed through the mouth can exit 
through these holes in the neck, and except that the arteries 
branch into an intricate capillary system in the arches, and 
thus are able to exchange oxygen and carbon dioxide more 
effectively with the water, the arrangement is identical. 

The conclusion is unavoidable. Our whole neck region, 
including these arterial arches just described, develops first 
in a fashion appropriate for a gill-breathing fish, and then is 
re-adapted by extensive remodeling for breathing in the air. 

The heart 

The heart, too, has been revised in the meantime. From a 
simple pulsating blood vessel, it is first improved by a devel- 
opment into two chambers. The first, receiving blood from 
the veins, is rather thin-walled; the second, at first nearest the 



head, pumps the blood out through the arches, and its walls 
grow much thicker and more powerful. A valve which pre- 
vents any back-flow of the blood is formed where the trunk 
vein enters the heart, and another at the exit into the aorta. 
As the heart lengthens faster than the body, it becomes coiled 
into a complete loop, so that the ventricle, the thick-walled 
chamber, no longer lies nearest the head (Fig. 79). 


to a row 






Fig. 79. Diagram of the human heart at the end of the fourth week of 
development, when it is in a simple two-chambered condition, in the shape 
of a loop consisting of a chamber (atrium) into which the trunk vein (sinus 
venosus) empties through a valve, and a second chamber (ventricle) opening 
into the aorta. 

This two-chambered heart is as far as fishes ever get, except 
the lungfishes, and for the requirements of a fish it is ideal. 
All the blood from the body is pumped to the gills for a 
fresh load of oxygen and a removal of carbon dioxide, before 
it passes to the organs of the body. 

How can such a pumping organ be transformed into one 
just as efficient for a double circuit? That is the problem of 
our circulatory development. Blood from the body must, 
after birth, be pumped to the lungs; and blood from the 
lungs must be kept separate and pumped out to the rest of 
the body. This involves a division of the heart into essen- 
tially two hearts, side by side. A partition grows down 
through the heart— its beginning may be seen in Fig. 79— to 
the left of the opening of the trunk vein. Another partition 


grows up from the bottom of the ventricle and connects with 
the spiral partition which has separated the aorta from the 
arteries to the lungs. Valves then develop between the two 
chambers on each side of the heart. In this way blood from 
the left ventricle is pumped into the aorta and that from the 
right ventricle goes into the pulmonary (lung) arches. 

In the lungfishes and Amphibia (frogs and toads, newts and 
salamanders), animals which have become only partially 
adapted to air-breathing, the first of these partitions forms, 
but the second does not. This is also true of most reptiles. 
Except for the Crocodilia, which have both partitions, al- 
though imperfect and perforated, only birds and mammals 
have four-chambered hearts. 

Before birth, however, our lungs are not functioning. 
Some blood goes to them, but much of what flows through 
the pulmonary arches passes through the still persisting con- 
nection to the aorta. The left side of the heart would there- 
fore receive less blood, and the aorta would also be rather 
empty, were it not that the partition between the two upper 
chambers of the heart remains incomplete, so that blood from 
the right side passes over to the left. As a matter of fact, there 
are actually two incomplete partitions, growing from oppo- 
site sides, with their openings slightly overlapping (see Fig. 
80). Most of this blood passing through the openings in the 
partitions has come directly from the placenta and is well 
oxygenated. It is thus shunted directly to the head and body 
without having to pass first through the lungs. 

At birth, as the lungs are inflated, the connection of the 
pulmonary arch on the left side to the dorsal aorta is shut off 
(see Fig. 78) and all the blood from the right side of the heart 
is shunted to the lungs. The blood returning from the lungs 
to the left side of the heart thereafter keeps the left auricle 
filled. The pressure against the two partitions holds them to- 
gether until they grow into one. The gap closes and the two 
sides of the heart are thus completely separated. Whenever 
this gap remains incompletely closed, the double circuit of 







To lungs 




Fig. 80. Diagram of the human heart in a six- to eight-weeks-old embryo. 
It is in a four-chambered condition. There is a double partition between the 
two auricles, each partition with an oval aperture in it. The state as pic- 
tured persists until birth, with the exception that the trunk vein is taken into 
the right auricle and its valve disappears and that the two pulmonary veins 
emptying into the left auricle are absorbed by its growth past the points at 
which they each fork, so that four, instead of two, pulmonary veins enter the 
mature left auricle. After birth the two partitions between the auricles 
coalesce, and the passage of blood between the latter is blocked. The circuit 
of the blood through the heart, indicated by the arrows, remains essentially 

the blood through the heart is imperfect. This happens in 
about one baby out of four, but only rarely is it so serious 
that enough blue blood leaks through from the right side to 
the left to tinge with blue all the blood going to the body. 
These rare "blue babies," or "mourning babies," as they are 
commonly called, usually die from lack of sufficient oxygen 
in the blood going to the body. 


We have already seen that after four weeks of development 
the digestive tube reaches from mouth to anus, with two blad- 
der-like outgrowths, the yolk sack and allantois. Shortly after 



this a number of buds appear at various places along it, giv- 
ing rise to a number of pouches (Fig. 81). One of these buds, 
just in front of the yolk sack, enlarges to form the liver. It 



Tip of 






Caecum and. 

Allantoic — 





Anus - 

Fig. 81. Right half of a human embryo at about seven weeks of age, after the 
intestine has pushed a loop down into the umbilical cord and the cloaca has 
become divided into rectum and urogenital sinus. The pericardium is a sack- 
like membrane surrounding the heart. Magnification about 41^ diameters. 
(Redrawn with modifications from Arey's Developmental Anatomy, after Mall. 
Courtesy of W. B. Saunders Company) 

grows enormously and at nine weeks is by far the largest 
organ in the body. It grows about the umbilical vein, which 
then forms a meshwork of large thin-walled vessels within the 
liver. In this way the blood from the placenta, with its fresh 
load of food, is brought first to the organ which later assumes 
the function of changing sugar into glycogen for temporary 


storage. The veins from the intestine are also collected into 
a big vessel which runs through a similar meshwork of vessels 
in the liver. Thus at birth all is ready for the digestive sys- 
tem to supplant the placenta without upsetting the means 
developed for providing a temporary storage of carbohydrate 
in the liver. 

The blood from the placenta or, after birth, from the small 
intestine brings to the liver a supply of amino acids. Such 
of these as are required for the synthesis of proteins are car- 
ried through the liver and distributed to the body cells. But 
amino acids are also used to supply energy through oxidation. 
Before the latter use can be made of them, the amino groups 
must be removed from the amino acid molecules. This is 
done in the liver, and ammonia is produced. The ammonia 
is then used in neutralizing various acids that are formed in 
metabolism. A large portion of the ammonia unites with car- 
bon dioxide to form urea. This waste product is carried by 
the circulation back to the placenta or, later on, to the kid- 
neys, whence it is excreted. 

These are not the sole functions of the liver. Another vital 
one is its role as an excretory organ. The red blood cor- 
puscles can function efficiently only for two or three weeks 
—then they ''wear out" and must be replaced. The task of 
the removal of the aged ones falls to certain cells in the liver. 
These, like the white blood cells, live and move freely about 
in the blood vessels. Unlike the white blood cells, they stay 
within the limits of the liver, and, instead of ingesting bac- 
teria, they prey upon ageing and worn-out red blood cells. 
These are broken down, and, while the iron of the hemoglo- 
bin is largely saved for re-use, other parts of the pigment are 
converted into bile pigments, greenish in color. From three 
months on, bile is being secreted. From the neck of the duct 
connecting intestine to liver there also grows a side pouch. 
This is the gall bladder, which stores the bile temporarily. 
After birth, whenever food enters the intestine from the stom- 
ach, bile will be released and mixed with it. Organic salts in 


the bile help to break up fats into smaller droplets, thus aid- 
ing the action of the digestive enzymes. 

Two other small pouches bud from the digestive tube 
close to the outgrowth that makes the liver and gall bladder. 
One is very close to the liver bud; the other is on the back 
side. These bend around until the glands that grow from 
them fuse into a single flat, lumpy pancreas. This gland has 
secreting cells which are ready to produce some of the prin- 
cipal enzymes used in digestion after birth. 

Other parts of the pancreas are of more immediate impor- 
tance. These are groups of gland cells, the islets of Langer- 
hans, which secrete their product into the blood rather than 
into the ducts leading to the intestine. This substance is 
insulin, and it regulates the concentration of sugar in the 
blood, both by controlling its use in the cells and by its stor- 
age, through conversion into glycogen, in the liver. 

Meanwhile the intestine itself has done some extensive 
growing. At four weeks it curls directly around into the tail, 
but by five weeks it has lengthened so much faster than the 
body that it forms a big loop, while the extension into the 
tail has disappeared. About halfway from the liver bud to 
the anus, a little pouch (the caecum) appears which marks the 
place where the small intestine will enter the large intestine. 
The tip of this little pouch becomes the appendix. The yolk 
sack is pinched off from the gut, and a partition separates the 
allantois and urinary bladder from the gut, as has already 
been described. At ten weeks the anal membrane ruptures, 
and the digestive system finally becomes a tube, the mouth 
having been opened considerably earlier. The layer of meso- 
derm around the digestive tube forms a double muscle layer, 
with fibers running circularly and lengthwise. With rhyth- 
mic wavelike contractions called peristalsis, these will push 
the contents of the intestine along as the food is digested and 
absorbed. Glands, too, are formed in the endodermal lining 
of the intestine. Some of these, mainly in the large intestine, 
secrete a slimy mucus which lubricates the intestine. (Water 


is principally absorbed from the large intestine; and as the 
contents become more and more solid, additional lubrication 
is required.) In the small intestine the glands secrete intes- 
tinal digestive juice, containing enzymes complementary and 
supplementary to those of the pancreas. 

The lining of the small intestine becomes covered with 
millions of small projections that make it look like velvet. 
These are the villi, which will absorb the digested foodstuffs. 
They greatly increase the absorbing surface of the intestine. 
Each villus has a central vessel filled with lymph, a fluid essen- 
tially like blood plasma. All these lymph ducts are gathered 
into a great central duct which traverses abdomen and chest to 
enter the large vein from the left shoulder, providing for future 
use a direct route to the center of distribution for the absorbed 
fatty acids and glycerin, quickly recombined into fats. Each 
villus also contains a capillary network which enables the 
sugars and amino acids, absorbed directly into the blood, to go 
immediately to the liver (see pp. 269-270). 

Above the buds of liver and pancreas a swelling in the 
digestive tube makes its appearance. This enlarges to form 
the stomach. Its inner lining becomes wrinkled and folded 
even more than that of the intestine and comes to contain 
thousands of gastric glands, able to secrete hydrochloric acid 
and the digestive enzyme pepsin, which begins the work of 
protein digestion. The stomach muscles wax extremely thick, 
and indicate what will be the chief action of the stomach on 
food, that of churning it and breaking it up mechanically 
into small particles which the digestive juices in the intestine 
can readily attack. Around the junction of stomach and small 
intestine an exceedingly strong ring (sphincter) of muscles 
develops, controlling the exit of food from the stomach and 
generally letting it through only in small amounts, after it 
is sufficiently broken up. This food is, of course, acid in 
reaction. Gland cells sensitive to acid develop in the upper 
part of the small intestine, where, when stimulated, they will 
secrete a substance into the blood. This substance, secretin, 


when carried to the pancreas and liver, starts the flow of pan- 
creatic juice and bile from those organs. All of this digestive 
apparatus is ready for work before birth, although, to be sure, 
it can handle only milk at first, and must gradually become 
accustomed to other foods. This is true for all mammals, but, 
as we have no doubt observed, the young of birds or lower 
vertebrates can handle adult foods immediately after hatching. 

The pharynx and its outgrowths 

The part of the digestive tube just back of the mouth is the 
pharynx. It produces a number of important pouches (Fig. 
82). Hindmost of these is a ventral pouch which elongates in 
measure with the narrow esophagus, that part of the diges- 
tive tube connecting pharynx and stomach. During the fourth 
week this lengthening pouch forks, and the two buds on the 
ends rapidly enlarge into lungs. These will be discussed more 
fully in connection with respiration. 

In front of this, five pairs of pouches bud out on the sides 
of the pharynx, the largest pair nearest the mouth. These 
are the gill pouches we have spoken of in connection with the 
aortic arches. Between the first pair of pouches another ven- 
tral pouch buds off to make the thyroid gland, which soon 
loses its connection with the pharynx. 

We have, of course, no use for gill pouches as such. Dur- 
ing the second month of our development, they either are 
modified into useful structures or degenerate entirely. The 
first pair of pouches, nearest the mouth, alone remains recog- 
nizable. These grow in length, keeping up with the thicken- 
ing of the head, until they form on each side a slender tube 
ending in a larger cavity just over the primitive ear. The cor- 
responding external pockets, or grooves, also deepen to form 
the ear pits. The region separating the ear pit and the inner 
pouch becomes modified into an eardrum of three layers, two 
of epithelium with a fibrous layer sandwiched in between 
them. After birth the Eustachian tubes from the pharynx to 
the ear cavity beneath the drum will be very useful in equal- 



Outline of 
Thyroid Gland- 

Furrow 1 


Furrow 2 

Bud of. 




Pouch i 

Wk, Pharyngeal 
Pouch 2 

~~ . Pouch 3 

Pouch 4 


Pouch 5 

Left Lung 


Dorsal portiori__ 


Right Lung 



Fig. 82. Reconstruction of the upper digestive tract of a six-weeks-old (12 
mm.) human embryo, seen in dorsal view, so as to show the outgrowths of the 
pharynx. The thyroid gland, located on the ventral side, is indicated only by 
its outline. (Redrawn with modifications from Arey's Developmental Anat- 
omy, after Hammar. Courtesy of W. B. Saunders Company) 


izing the air pressure on the two sides of the eardrum, but 
they are also a source of considerable trouble, since they pro- 
vide an entrance for germs into the ear. Especially in babies, 
when these tubes are relatively short, this is the source of 
many earaches. 

From the tips of the second pair of pouches grow the two 
tonsils located on the sides of the pharynx. They are lymph 
glands, of which there are great numbers in the body, and so 
individually are not of vital importance. 

From the fore tips of the third and fourth pairs of pouches 
develop four little pea-sized glands. In the adult* these come 
to lie just behind, or buried within, the thyroid. They are 
the parathyroid glands, of vital importance in controlling the 
concentration of calcium in the blood. 

From the hind tips of the third and fourth pairs of pouches 
there grow glands which fuse to make the large thymus. The 
function of this organ is somewhat of a mystery, as it is largest 
before birth and steadily decreases in size thereafter. (Some- 
times in babies it is so large it hinders breathing and must 
be reduced by x-ray treatment to avoid suffocation.) It is 
thought to regulate growth and development during the em- 
bryonic period and infancy, for later its removal is not serious. 

Nothing of importance is known to develop from the fifth 
pair of pouches. 

In all but the first pair, the corresponding external grooves 
or pits fill in and disappear. Only rarely does the membrane 
between external groove and internal pouch rupture, so as 
to make a hole entirely through the neck into the pharynx. 
Sometimes a cyst in the neck is formed from incomplete 
obliteration of one of the external clefts. 

The tongue forms as an extension of the muscular floor of 
the pharynx, and grows forward into the mouth. 

The mouth 

In the fourth week of life the digestive tube breaks through 
the body surface to form a mouth. It is at first just a hole. 



There are no jaws. Three pairs of pouches grow from its 
walls to make the three pairs of salivary glands. These will 
secrete a watery fluid of value in lubricating the food for 
swallowing and also containing an enzyme, ptyalin, which 
acts on starches. 

Teeth begin to form at two and one-half months. Gland 
cells from the lining of the mouth begin to secrete the hard, 


Fig. 83. The early development of a tooth— an incisor at the seventh (pre- 
natal) month. Magnified about 38 diameters. (Redrawn with modifications 
from Arey's Developmental Anatomy, alter Tourneux. Courtesy of W. B. 
Saunders Company) 

white enamel, and other cells from the mesoderm secrete the 
inner, softer dentine and the cement (Fig. 83). The jaw grows 
up on either side of the developing teeth until they are en- 
closed in a trench. Then bony ridges form between them, until 
each tooth is in its individual socket. When at length the 
crown of the tooth is complete, the enamel-forming organ 
degenerates, but the pulp which has been forming dentine 
remains in the tooth, a mixture of blood and lymph vessels 
and nerve fibers in a web of connective tissue. This is the 
live part of the tooth, commonly called its nerve. The time 
at which the milk teeth are cut varies with climate and nu- 
trition and also genetically. But they usually follow a fairly 


definite sequence, the middle incisors appearing first, in the 
sixth to eighth month after birth, and then the lateral in- 
cisors, the first molars, and the canines. Last come the sec- 
ond molars, often not until the third year. Reptiles have 
numerous sets of teeth which replace one another as their 
earlier sets are worn out, but we ourselves are limited to 
one replacement. The beginnings of the permanent teeth 
develop underneath the milk teeth and are already present 
one to three months before birth. The two extra molars of 
each jaw are developing even earlier, but the wisdom teeth 
are delayed until we are five years old. 

From the back of the future mouth a small pouch grows up 
against the brain and is shut off. A pouch grows down from 
the brain just behind it, and the two together make up the 
important pituitary gland, whose control over growth, female 
sexual cycles, and other vital phenomena is of great impor- 
tance and will require a whole discussion for itself. 

A partition grows across the mouth from the sides, sepa- 
rating an upper nasal cavity from the mouth proper. This 
partition is the palate. The nasal cavity connects with two 
pits in the face to make the nostrils. The palate does not 
extend all the way back, so nasal cavity and mouth still 
connect at the beginning of the pharynx. 


Just as in the case of the digestive system, where we saw 
equipment for handling food provided long before the time 
when food first has to be handled— so here. A system for 
breathing air, for providing an adequate supply of oxygen 
to the blood, develops long before the moment when air first 
inflates the lungs, just after birth. 

Already the body has developed the rudiments of a more 
primitive type of respiratory system, only to junk it. The 
aortic arches, the paired pouches along the pharynx, the cor- 


responding external clefts, and the supporting bars of cartilage 
in the neck (of which more will be said in connection with 
the skeleton)-all these resemble parts of a gill system, like 
that of a fish, suitable for exchanging oxygen and carbon 
dioxide between blood and surrounding water. All the land- 
living, air-breathing animals develop a primitive gill system 
of this sort, and of them all only the amphibians ever use it 
for respiratory purposes during any stage of their lives. 

In following the development of the digestive system, we 
learned of the origin of windpipe and lungs from a ventral 
bud on the pharynx. Fishes, while they lack lungs, develop 
such a structure too, though rarely forked. In only a few 
of them, however, is it of any help in breathing; and in 
most it serves as an air bladder which, when filled, makes the 
fish more buoyant, and when empty, heavier; and so helps the 
fish to rise or sink in the water with very little muscular exer- 
tion. Its use as a lung depends mainly on an abundant blood 
supply, on a tremendous exposure of blood to air in multi- 
tudes of capillaries spreading over a great surface. Only a 
few fishes, the lungfishes, are thus equipped. These are 
fresh-water fish, living in lands of frequent drought; and 
their ability to breathe air directly may frequently save their 

lives. 6 

The development of our own lungs follows the lines just in- 
dicated. The windpipe, or trachea, forks into two bronchi, and 
these in turn branch into numerous bronchial tubes. These 
branch again and again to form the multitudes of pouches 
in the lungs. The pulmonary pair of aortic arches sends ar- 
teries to these, arteries which branch into capillaries whose 
thin walls make up most of the surface of the air sacks. Thus, 
once all the blood from the right side of the heart is directed 
into the lungs-this, you remember, happens for the first 
time at birth-all the blood making the circuit is exposed to 
the air in the lungs. In about twenty seconds the blood 

6 H. W. Smith has written entertainingly of the lungfishes and their place 
in philosophy in Kamongo (Viking Press, New York, 1932). 


coursing through the lungs makes the journey from the right 
side of the heart back to the left. In the remainder of each 
minute it makes the circuit of the body and is back at the 
heart again, ready for another trip to the lungs. During the 
twenty seconds in the lungs the blood must lose most of its 
content of carbon dioxide and pick up a fresh load of oxygen. 

Rapid work-it could be done only if the blood were ex- 
posed to a maximum extent. That means a lot of surface! 
The structure of the lungs is simply a means of exposing to 
the air as great a surface as possible, while keeping the organs 
reasonably compact and away from the danger of evaporation. 

The gas exchange takes place by diffusion. Oxygen will 
pass into the blood because it is less concentrated there; and 
carbon dioxide will pass from the blood into the air, follow- 
ing its concentration gradient. Remember, however, that 
for substances to diffuse through a differentially permeable 
membrane, they must be dissolved. If the membrane, there- 
fore, were not moist, diffusion would stop. This is sufficient 
reason for the internal situation of the lungs. Were they as 
exposed to the air as are the gills of a fish when it is taken 
out of the water, they too would speedily dry up and the gas 
exchange would stop. This is why a fish suffocates in air. 

Because of the long passages through which the air must 
pass before it reaches the lungs, twisting ways through the 
moist nose, trachea, and bronchi, the air is thoroughly 
humidified before it reaches the air sacks, and has little dry- 
ing effect. Nor is this the sole type of air conditioning pro- 
vided. Certain cells lining the nose and trachea secrete slick 
mucus, which entraps dust particles and bacteria, while other 
cells, equipped with cilia, beat this phlegm up into the throat 
and nose where it can be eliminated. 

Just back of the tongue grows a little flap called the epiglot- 
tis. Every time we swallow, the larynx moves up under the 
base of the tongue, and the back of the tongue pushes the 
epiglottis down over the opening to the trachea, providing 
an automatic guard against getting food into the lungs. This 


is also prevented by a potent set of nervous reflexes, which, 
whenever a crumb gets past the epiglottis, starts a vigorous 
coughing. The danger is not primarily one of suffocation, 
but of infection. The lungs, warm and moist, are ideal abodes 
(from the germ's point of view). Food nearly always carries 
hordes of bacteria, and it becomes a matter of great impor- 
tance to prevent their access to the delicate lungs. 

The danger of suffocation is prevented in another way. 
Incomplete rings of cartilage develop one above the other, 
in the walls of the trachea and bronchi. These act as springs 
and serve to keep the passages always open. 

Voice production 

The upper part of the bud that produces the trachea and 
lungs becomes enlarged into a voice-box, the larynx. A pair 
of folds grows from its sides. These are the vocal cords. They 
can be stretched through the pull of muscles on cartilages in 
the walls of the larynx. When they are taut, air passing up 
from the lungs causes them to vibrate and produce a sound. 
Like strings, the tighter they are stretched, the higher pitched 
the sound. 

During adolescence the vocal cords lengthen and thicken, 
and the whole larynx enlarges, especially in males. This is 
responsible for the change in voice at this period; for the 
longer and thicker a vibrating string, the deeper its tone. 

Sounds from the larynx are shaped by the regulation of 
the mouth and throat into one or another of the vowels, 
and the tongue, teeth, and lips provide the various stops we 
call consonants. The resonance (tone quality) of a voice de- 
pends on the vibration of the sound in the nose, in the 
sinuses (hollow spaces) of cheekbones and forehead, in the 
throat and chest. All these are under voluntary control, 
which means years of effort and practice before we can reach 
the peak of skill in speech and singing. In the long road of 
growth and development birth is but a bend, not a beginning 
or an end. 



The first time our vocal mechanism is used is when we 
are ushered from the warm, dark shelter of our mother's body 
into the harsh brightness and cold of a new world. The 
reflex reaction to gasp and cry at this moment provides the 
usual impulse that starts the breathing mechanism func- 

The lungs themselves are not muscular. How is the air 
in them, then, constantly replenished from outside? A frog 
simply closes its nostrils and swallows a gulp of air, but this 
method would not be effective for our greater needs. 

The degree of inflation or deflation of the lungs depends 
on the equilibrium between their internal and external 
pressure. Their internal pressure is virtually that of the 
atmosphere, over which we have no bodily control. Their 
external pressure, however, is that of the chest cavity in 
which they lie, and since this is sealed we can control it. 
By upward and downward movements of the diaphragm, 
a dome-shaped muscle separating chest from abdomen, the 
pressure in the chest cavity is varied. When chest pressure 
increases above atmospheric pressure, air is expelled from the 
lungs and they deflate. When it falls below atmospheric 
pressure, air flows into the lungs and they are inflated. This 
muscular diaphragm is a unique characteristic of mammals. 
It develops from various parts of the thin layer of mesoderm 
that lines the body cavity and forms slings supporting the 
internal organs. In all vertebrates there is a transverse parti- 
tion separating a space surrounding the heart from the re- 
mainder of the body cavity. In both birds and mammals 
an additional fold grows in from the sides and back of the 
coelom and separates off the chest and cavity; but only in 
mammals do muscles grow into this membrane, chiefly by 
migration from the neck, and convert it into an effective part 
of the breathing mechanism. Here again our own develop- 


ment resembles that of a reptile, only to go considerably 

Since muscles work only when they contract, and the con- 
traction of the diaphragm increases the volume of the chest 
cavity, the diaphragm produces only inspiration directly. Ex- 
piration occurs when the abdominal muscles contract and 
push the internal organs up against the diaphragm. In its 
task the diaphragm is assisted by the rib muscles. The ribs 
slant from the backbone down toward their attachments to 
the breastbone. When the muscles between them contract, 
the ribs are pulled up in front. This deepens the chest and 
increases its capacity. The air pressure inside falls, and the 
lungs correspondingly expand. 

Some babies cry a lot, but we should recognize that this 
may have its advantages. After a system commences to func- 
tion, its further development and growth are very largely 
conditioned by the use it gets, and this is especially true of 
systems under voluntary control. Hence the value of exercise 
and practice. As the baby is growing rapidly, its breathing 
needs are constantly greater, and vigorous exercise of the 
breathing mechanism may help it to supply the demand by 
furthering its own growth. 


If the development of the circulatory and respiratory sys- 
tems has seemed strangely roundabout, what impression will 
that of the excretory system make? For here the remodeling 
that goes on is even more extensive. Only with the third at- 
tempt are the final kidneys produced. 

The excretory system starts to form in the neck region, in 
the seventh to the fourteenth mesodermal segments shortly 
after these are blocked out. Branches from the trunk arteries 
here pass in pairs to the walls of the body cavity, and each 
makes a little ball of capillaries situated in a hump projecting 



out into the cavity. The wastes of metabolism, except carbon 
dioxide, which is eliminated through the lungs after birth, 
are thus brought by the blood to these humps, and there 
filter into the body cavity. Tubules (tiny tubes) grow in 
each segment from the body cavity into the mesoderm, and 
each then turns rearward to connect with the tubule in the 
next segment (see Fig. 84). Thus a duct is formed through 
which fluid wastes might pass all the way to the rear and 
empty into the cloaca. 

Neural Tube 








Fig. 84. Development of the tubules and duct of the head-kidney. A, ante- 
rior level of the embryo, with tubules and duct completed. B, posterior level, 
where tubules are still budding and linking together. (Redrawn with modifi- 
cations from Arey's Developmental Anatomy, after Felix and Burlend. 
Courtesy of W. B. Saunders Company) 



Since this most primitive excretory system begins to de- 
velop so far forward in the body, it is called the head-kidney. 
Segmented worms and Amphioxus, the lancelet, never get 
past a somewhat similar stage in the development of excre- 
tory organs. But this type of system has some pronounced 
disadvantages: The coelom is ineffective in collecting wastes 

tubule -^ 






tubule v 







Fig. 85. A, cross section of a four-weeks-old (5 mm.) human embryo in the 
region of the mid-kidney, showing the form and relations of a mid-kidney 
tubule. B, cross section of the left urogenital ridge in a five-and-a-half-weeks- 
old (10 mm.) embryo, to show the character of a completed mid-kidney 
tubule and the relations of the mid-kidney duct and the female sexual duct. 
(Redrawn with modifications from Arey's Developmental Anatomy. Courtesy 
of W. B. Saunders Company) 

from those cells that do not line it, and the transfer of wastes 
from the balls of capillaries to the mouths of the tubules is 
indirect. A second consideration is that the number of ex- 
cretory tubules, if limited to one pair per body segment, 
might be altogether too few for a bulky animal. 

Our next step in developing an excretory system obviates 
one of these disadvantages (Fig. 85). The mesoderm around 
the upper (dorsal) surface of the body cavity grows down 
like a cup to enclose each ball of capillaries. The wastes are 
then taken directly from the blood into the excretory tubules, 
and the body cavity loses all excretory function. Thence- 


forward it is nothing but a space where organs may grow and 

The cells of the part of each tubule next to the capsule 
(the ball of capillaries and the cup around it) become tall 
and columnar, typical secretory cells. They extract the useful 
substances from the urine and return them to the blood, and 
also add to the urine certain protein wastes, unremoved by 
simple filtration. 

This change in the type of excretory tubule takes place, 
however, only in the segments from the fifteenth on. The 
seven pairs of tubules in front of this, making up the head- 
kidney, degenerate completely before becoming functional. 
There are some eighty pairs of the new sort making up the 
second or mid-kidney. At any one time, however, not more 
than thirty to thirty-five pairs are present, for those in front 
begin to degenerate even before those in the rear segments 
have formed. 

Although far more effective than the head-kidney, the 
mid-kidney, too, is inadequate for our needs. It serves well 
enough in fishes and amphibians, but in land animals it too is 
junked, like the head-kidney, although a part, here and there, 
is salvaged and turned to some new use. The majority of 
the tubules in each mid-kidney degenerate, but in males the 
two ducts remain and are utilized by the reproductive organs. 
In males, too, a number of tubules in the neighborhood of 
the testes are salvaged and used for storing sperms. 

In the fifth week, each hind-kidney begins to form as a bud 
from the duct of the mid-kidney on each side (Fig. 86). Each 
bud appears just above the point where the mid-kidney duct 
it grows from enters the bladder. Each bud lengthens into a 
tube, or ureter, with a flared end, the pelvis, or collecting 
portion, of each kidney. From the pelvis of each kidney grow 
numbers of branches and into these empty tiers of excretory 
tubules, each similar to a mid-kidney tubule. There are 
about a million of these to each hind-kidney! 

The gain in effectiveness through the development of the 


Allan to is- — — 



Coelorn—-^ ^-Rectum 




Fig. 86. Development of the hind-kidney and ureter, at about six weeks. 
Magnification about 30 diameters. (Redrawn with modifications from Arey's 
Developmental Anatomy, Prentiss, after Keibel. Courtesy of W. B. Saunders 

hind-kidney is chiefly in the enormous increase in number of 
the tubules and in their more compact arrangement, which 
simplifies the problem of distributing the blood to them and 
of carrying off the urine. 

The bladder and urethra 

The cloaca is partitioned off from the hind-gut in the 
seventh week of development (Fig. 87). Of the allantoic por- 
tion, the upper part, beyond the point where the mid-kidney 
ducts and the ureters enter, becomes the urinary bladder. 
The lower part, which serves as a duct to carry off the urine 
and, in the male, the sex cells, is the urethra. This opens, at 
first, on the underside (posterior) of a hump, or tubercle, 
that begins to grow out from the body just in front of the 
tail. The further development of this region will be con- 
sidered later along with the development of the reproductive 


_ — _ Sonad 


Fold — 







A Mid- kidney 
mr~ Duct 



Fig. 87. Relations of the urinary bladder, urethra, and sexual ducts in a 
human embryo of nine weeks, following division of the cloaca. Magnification 
about 19 diameters. (Redrawn with modifications from Arey's Developmental 
Anatomy, Prentiss, after Keibel. Courtesy of W. B. Saunders Company) 


Circulation, digestion and absorption, respiration, and ex- 
cretion— these activities are immediately concerned with the 
vital supply of energy and materials for the organism. We 
need also to be continually aware of changes in our environ- 
ment, so as to make appropriate adjustments, secure food and 
water, protect ourselves, find a mate, enjoy living. The 
sensory receptors that make these activities possible must all 
be provided for before birth, although we must learn there- 
after how to interpret what they tell us. 

We probably think that we depend chiefly on sight and 


hearing, but we would be in a worse way without an ade- 
quate sense of equilibrium, of directional movement, or of 
muscle tone (the degree to which each muscle is contracted). 
Pain is an efficient guardian, and the more specialized senses 
of heat, cold, and pressure assist in avoiding injury. Hunger 
and thirst are potent reminders of nutritive needs. Taste and 
smell provide discrimination and warning as to food and 
drink. All these have their special sense organs. 

The sense organ of pain is the simplest, being merely a 
branched nerve-ending. The organs of heat, touch, and cold 
have bulbs of connective tissue around branched nerve- 
endings, increasing the range of their sensitivity. All of these 
are widely but unequally distributed over the body. They 
are especially concentrated in the hands and fingers. On the 
palms and finger tips, as in similar locations on the feet, the 
skin produces fine ridges which are so individual in character 
that we can be identified by them. Everi identical twins. have 
different fingerprints, a good indication of the ever-present 
differences in environment in which our genes must operate. 

On the tongue grow taste buds, little groups of cells sunken 
under the surface, each equipped with a tiny hair. Different 
areas of the tongue become predominantly sensitive to differ- 
ent tastes, sour, sweet, salty, bitter. We may conjecture that 
there are four different kinds of taste buds, and that their 
distribution accounts for the various taste areas on the 

While we are largely ignorant as yet of the genetic factors 
back of these taste and odor discriminations, it has been 
found that some 30 per cent of our population cannot taste 
phenyl-thio-carbamide at all, although to the remainder it 
has an intensely bitter taste. This instance of taste blindness 
is due to a recessive gene. More recently it has been discov- 
ered that there are a number of different taste reactions to 
mannose, a sugar, and these too are inherited. 

Ciliated sensory cells are also produced in the nose. These 
are amazingly delicate in the perception of certain odors, and 


the variety they can distinguish seems to be well-nigh un- 

The eye 

The paired eyes begin as stalked outgrowths, or vesicles, 
from the underside of the forebrain. 7 When each outgrowth 
reaches the skin, it forms a cup, and acts as an organizer for 
the ectoderm lying over it. The latter makes a little pit cor- 
responding to the cup. Next, the pit closes over, and thus a 
little hollow ball of ectoderm is left. The cup develops into 
the retina, and the ball becomes the lens (Fig. 88). 

In its specialization, the retina becomes differentiated into 
quite a number of layers. In the deepest layers are odd-shaped 
cells known as rods and cones, while the surface layers are 
made of nerve cells whose long projections extend over the 
surface of the retina to the origin of the optic nerve, in 
which they mount to the brain. The rods and cones are the 
special cells which are light-sensitive. The rods are distrib- 
uted over the entire retina except at the very center, while 
the cones are absent around the rim. Both are lacking where 
the optic nerve enters-this is a blind spot. The rods are 
more responsive to faint light but cannot distinguish colors, 
so that in twilight or moonlight, when we see solely through 
the responses of the rods, objects are poorly denned and color 
is lacking. The cones provide us with our most distinct 
vision, and can discriminate between the three colors, red, 
green, and violet, of which all others are mixtures. (There 
are probably three distinct kinds of cones, each with maxi- 
mum sensitivity for one of the three primary colors.) 

7 In addition to the pair of functional eyes, man possesses the vestige of a 
primitive third eye, originally located on the top of the head, where an eye 
would have been useful to primitive vertebrates living on the ocean floor. 
This vestige is the pineal body, a small outgrowth from the forebrain (see 
Fig 102). Some lizards still have a pineal eye, with lens and retina, buried 
beneath the skin. In man, the pineal body has not been shown to have any 
functional value, although it has been suspected of being a gland. The great 
French philosopher and mathematician Descartes thought it might possibly 
be the seat of the soul. 



Fig. 88. Stages in the development of the retina and lens of the eye. (From 
Goldschmidt's Ascaris. Courtesy of Prentice-Hall, Inc.) 


The retina, with the lens, secretes the jelly, the vitreous 
humor, which fills the hollow of the eyeball, and helps to 
keep it in shape and the retina in place. The part of the 
outer layer of the optic cup lying behind the retina becomes 
a thin layer which accumulates quantities of a black pigment 
that absorbs light, preventing its reflection and any conse- 
quent blurring of the image. From the rim of the optic cup 
there form the ligaments which suspend the lens and the 
major portion of the iris, including its pigmented layers and 
the radial and circular muscle fibers which respectively dilate 
and constrict the pupil— the hole in the center of the iris. 

During development the lens gradually changes from a 
hollow to a solid ball. This is accomplished by the elonga- 
tion of the innermost cells, as shown in Fig. 88. The inner 
cells thus become the transparent fibers of the lens. The 
blood vessels which supply the lens during its early develop- 
ment have degenerated completely by birth. The course 
of the large vessel that supplies the back surface of the 
lens is marked by the hyaloid canal through the vitreous 

The lens of the eye is a light-collecting device, bringing all 
the light entering the eye from any one source to a focus at a 
single point on a sensitive screen, the retina. No image could 
be formed without a lens, unless the entrance of light were 
limited to a pinhole in size, and then the amount of light 
that could enter would generally be too faint to stimulate 
the cones and, perhaps, even the rods of the retina. We 
would certainly see no gorgeous colors; everything would be 
dim as in faint moonlight. In animals like the flatworm, in 
which we find eyes, but no lenses, there can be no real vision 
whatever, for no images can be formed. The worm is merely 
sensitive to varying degrees of light and darkness. 

In the human eye, the lens is not the most powerful light- 
gatherer (see p. 293). It is, nevertheless, of prime importance 
in vision, for it furnishes the means whereby we accommo- 
date for distance, that is, whereby we focus our vision for 



objects close to us or far away. This is accomplished by an 
actual change in the shape of the elastic lens. When the 
fibers suspending the lens become looser, the lens becomes 
rounder and focuses on near-by objects. When the sus- 
pensory fibers become taut, the lens is pressed flatter and 
distant objects are brought into focus. Very quickly during 
the growth of the eyeball, the lens is brought to just the 
proper distance from the retina to cast the image onto the 

Ciliary 2. 











Fig. 89. Diagrammatic section through the mature human eye. (Redrawn 
from Buchanan's Elements of Biology. Courtesy of Harper and Brothers^ 

One thing about the image should be noticed; it is com- 
pletely inverted. Experiments show that we do not inherit a 
mental ability to reinvert the picture of what we see, but that 
we must learn to do it through experience. Small reason for 
wonder that babies grope so wildly at first! To learn this for 
the first time must be quite a task. 

The rest of the eye (see Fig. 89), except for a thin outer 
membrane (conjunctiva) that is continuous with the eyelids, 
comes from the mesoderm. This forms two coats around the 
retina and lens and, in addition, produces the voluntary 


muscles which move each eye and pass from the eyeball to 
the bony socket. 

The inner mesodermal layer, next to the retina, is called 
the choroid coat. It is rich in the blood vessels which supply 
the eye. In front this layer contributes to the iris and the 
ciliary muscles. Owing to the manner of their attachment, 
contraction of the ciliary muscles loosens the suspensory 
fibers of the lens, and when the ciliary muscles relax, the 
suspensory fibers tauten. 

The outer coat of the eyeball is the tough white sclera, 
originating, like the choroid, from the mesoderm. It is the 
part we see in front as the white of the eye. Just over the 
iris it becomes transparent, and this portion is known as the 
cornea. It is lens-shaped and in man is more powerful than 
the real lens in gathering light. Also, being very tough like 
the rest of the sclera, it provides excellent protection. Be- 
tween it and the lens a watery fluid, the aqueous humor, 
accumulates, serving to prevent the refraction that would 
occur were the space air-filled, and that would decrease the 
power of the lens. 

Blindness results whenever the cornea becomes opaque. 
Congenital blindness (due to gonorrhea) is of this sort. The 
germ of this disease attacks the membranes of the vagina and 
the cornea by preference, and many a child is blind from 
birth on account of infection from its mother. There is 
no excuse for this today, as it is well known that a few drops 
of a silver nitrate or similar solution in the eyes of a new- 
born babe will effectually sterilize them. Most states in our 
country now require this by law. 

The ear 

The ear (Fig. 90) is really double in origin. The inner 
ear, the true sense organ, is formed from a pocket of the 
ectoderm overlying the brain. It later becomes buried deep 
within the skull. The remainder of the ear is an accessory to 
hearing and represents the salvage of various gill structures. 




Tympanic Cavity- 

Utriculus Cartilaginous 
" Temporal Bone 



•Eustachian Tube 

Fig. 90. The relations of the developing internal, middle, and external parts 
of the fetal ear at three months. The spongy tissue around the bones of the 
middle ear has yet to degenerate to produce the ultimate enlargement of the 
tympanic cavity of the middle ear. (Redrawn with modifications from Arey's 
Developmental Anatomy. Courtesy of W. B. Saunders Company) 

As related before, the first gill pouch becomes the Eustachian 
tube leading from the throat to the eardrum. The corre- 
sponding external cleft becomes the auditory tube, and the 
membrane between them is the eardrum. 

Around the opening of each auditory tube arise six little 
bumps (Fig. 91, 1-6) and a curving ridge (Fig. gi/4, af). 
These grow together to make the external ears. These super- 
ficial adornments should presumably function as an aid to 
hearing, as funnels to collect sound waves and reflect them 
in toward the drum. Actually their value in man is neg- 
ligible. One can hear practically as well with no external 
ears at all. If this is so, then what must one think of the 
presence of a complete set of muscles connecting ear and 
skull, capable only of wiggling the ears, and that only in an 
occasional person? Or of the internal muscles of the ear, 
which could cup our ears the better to pick up faint sounds, 
if only they were stronger and had functional nervous con- 
nections? The same muscles are wonderfully useful to a 



3 V 

Fig 01. Stages in the development of the human external ear. A, in the sixth 
week {ov, the inner ear). B, C, during the seventh week. D, adult (Redrawn 
from Arey's Developmental Anatomy, after His. Courtesy of W. B. Saunders 

donkey, and presumably in us must represent a heritage from 
some ancestor with bigger and better ears than ours. 

Within the cavity of the middle ear (that is, beneath the 
eardrum) there develop three little bones of peculiar shape 
(see Fig. 90). They are derived from the cartilaginous gill 
bars, which form in the flesh between the gill clefts, and 
which are quite essential, in fishes, for the support of the 
gills. Each of these gill bars is V -shaped, hinged at the apex, 
which points toward the rear. From the pair in front of the 
first cleft come the upper and lower jaws, the right and left 
sides of each growing forward until they meet in front. In 
the long-jawed fishes, amphibians, and reptiles, these jaws re- 
tain their original joint with the skull; but, along with other 
mammals, human beings form a new one farther forward, 
where the contraction of the jaw muscle has more favorable 
leverage, and can exert greater speed and power in snapping 
shut or clenching the lower jaw. This leaves the rear half of 


the primitive jaw useless, and most of it never turns to bone. 
But the very tips of the upper and lower jaws, at the original 
joint itself, lie close to the ear and are turned to a new use. 
They develop into the hammer and anvil, the first two of the 
chain of three little bones which bridge the middle ear and 
convey vibrations from the eardrum across to the inner ear. 
The third little bone, the stirrup, comes from the second 
gill bar, which in fishes braces the joint of the jaws against 
the skull. In amphibians and reptiles the upper jaw has be- 
come fused to the skull, and this service is no longer needed. 
Being conveniently placed, this gill bar was then utilized as 
the first earbone, originally stretching all the way from the 
eardrum to the opening of the inner ear. 

These three little bones play a part in intensifying the vi- 
brations, for they transmit them from a large membrane, the 
eardrum, to a small one at the oval window of the inner ear. 
Calculations show that this magnification is about ten times. 
The middle ear is thus a valuable aid to hearing. Up until 
the last fetal months, however, the spongy connective tissue 
in which the three little bones develop still fills the upper 
part of the chamber of the middle ear, as can be seen in 
Fig. go. This material must degenerate and free the move- 
ments of the bones before hearing can become acute. Since 
this process is not completed until after birth, newborn in- 
fants are deaf for some weeks. 

The Eustachian tube is helpful in equalizing the air pres- 
sure on both sides of the eardrum, thus preventing it from 
bursting. The middle ear has its disadvantages, however, 
since its connection with the mouth lends itself to infection, 
especially in babyhood when the passage is still very short. 
Not only is the middle ear itself an ideal haven for germs, 
but it lies close to the hollow mastoid bone of the skull. In- 
fections may spread to these air spaces, setting up painful 
inflammations that can be dealt with only by a delicate and 
dangerous operation, shaving or clipping away the bone until 


the cavities are exposed, and then draining and sterilizing 

them. 8 

The inner ear is a series of membranous sacks and canals, 
all filled with fluid and lying imbedded in the skull (Figs. 90, 
92). At first the inner ear is just a single sack, from which vari- 
ous outgrowths later emerge. The endolymphatic duct and 
sack are the vestiges of the original connection of the inner ear 
with the outer surface of the head. At the upper end of the 
central sack three disks grow out, each in a different plane, so 
that each is roughly at right angles to the other two. These 
disks grow thinner in the middle, and finally become hollow 
rings,*the semicircular canals. This most primitive part of the 
ear is concerned not with hearing but with a far more essential 
sense, that of equilibrium. At the base of each ring is a 
swollen bulb, lined with sensory cells bearing cilia. When 
the head moves in any direction, the inertia of the fluid in 
the canals causes it to produce pressure in a particular direc- 
tion upon these sensory "hair cells." Their excitation is 
transmitted over the auditory nerve to the brain and there 
combined into an interpretation (perception). Since each 
semicircular canal occupies a plane of space at right angles 
to the two others, any movement will affect one or more of 
the canals. 

The original central sack also becomes enlarged and partly 
separated into two, an upper utriculus and a lower sacculus. 
These, too, are sense organs of equilibrium, assisting the 
canals by informing us of the position of our heads even 
when they are still. In each of these chambers there is a clus- 
ter of "hair cells," and clumps of little "ear stones" (otoliths) 
of limestone attached to the hairs. In the utriculus the stones 
press vertically on the hairs; in the sacculus they hang lat- 
erally, producing a shearing pull upon them. Any change in 
the position of the head, therefore, alters the pressure or pull 

8 Recently word comes that the new sulfa drugs, already proved of great 
value in the treatment of so many ailments, may render these stern measures 
less frequently necessary. 

2 9 8 
















Fig. 92. For B see p. 299. 

of the stones on the sensory cilia, and keeps us informed as 
to "which end is up" (Fig. 92.B). 

From beneath the central sack there grows a long slender 
pouch, which coils at the tip until it looks like a snail shell. 
This is the cochlea, the real sense organ of hearing. It is 
rudimentary in fishes and amphibians and becomes coiled 
only in mammals. When its development is completed, the 


coiled cavity is divided internally by membranes into three 
passages, the original or central one closed off, the upper 
and lower, formed subsequently, communicating at the apex 
of the coil. All three are filled with fluid. Into the upper 
passage, the vestibular canal, opens the oval window against 
which the stirrup fits, so that vibrations of the latter are trans- 
mitted to the fluid in the passage. They then pass up to the 
apex of the coil and back down through the lower passage, 

Nerve Fibers 






Fig. 92. A, the inner ear. Redrawn with modifications from Buchanan's Ele- 
ments of Biology. Courtesy of Harper Sc Bros. B, the sense organs of static 
equilibrium in the inner ear. A stimulus is exerted upon the hair cells 
through the pull of gravity upon the otoliths attached to the little hairs. 
Tilting the head to left or right acts upon the sacculi of the two ears in an 
opposite way. Tilting the head forward or backward, or turning upside 
down, acts upon the utriculi. (Redrawn from Carlson and Johnson's The 
Machinery of the Body. Courtesy of The University of Chicago Press) 

the tympanic canal, ending at a little round window covered 
with a membrane, which takes up the vibration, preventing 
its being echoed back. If the coil of the cochlea were straight- 
ened out, it would appear as in Fig. 93. 

Separating the lower passage from the central enclosed one 
is the basilar membrane. Upon it rests a layer of sensory hair 
cells, firmly supported by skeletal rods, while above them 
hangs the tectorial membrane supported from one side. One 



-Middle Ear Vestibular 

Stirrup /-Canal 

s- Ova I Window I Cochlear 
( If Canal 

l Ti/mpanic 
f Canal 











Fig. 93. The organ of hearing. "Uncoiling" the spiral cochlea and making a 
cross section of it to reveal the relationships of its three canals. (Redrawn 
from Carlson and Johnson's The Machinery of the Body. Courtesy of The 
University of Chicago Press) 

widely accepted theory of hearing is that when the basilar 
membrane is thrown into vibration, these cells bob up and 
down, and the cilia are bumped against the overhanging 
membrane. At any rate, the hair cells are thrown into a state 
of excitation, and their stimulation is transmitted to the 
brain and interpreted as sound. 

The basilar membrane is tuned somewhat like a stringed 
instrument to sounds of various pitch. At the tip of the coil 


it is broad and at the other end narrow, varying gradually 
between, so that at the tip, like a long string, it responds to a 
deep tone, and at the other end, like a short string, to a high 
tone. Development proceeds from the base to the tip of the 


In the ear, a vibration of a particular frequency (number 
of waves per second) in the fluid of the lower passage sets the 
basilar membrane vibrating only at the point that is tuned 
to it. The stronger the vibrations, the more the sensory cells 
at the tuned level of the basilar membrane will be stimu- 
lated. In this way we hear some sounds faintly, and others 


The timbre, or tone color, of a sound is really due to a 
combination of tones. Whether or not this combination seems 
pleasing (harmonious) depends partly on certain mathe- 
matical relations between sound frequencies (multiples, for 
instance, are harmonious) and partly on learning. 


The skin and its glands 

The skin is a protection of no mean sort. The epider- 
mis, or outer layer (Fig. 94, epithelial cells), is a speciali- 
zation of the ectoderm. Underlying cells divide rapidly and 
the outer ones become horny and natter and natter as they 
are pushed to the outside. They soon die, and only their 
flattened horny shells remain to protect our living cells from 


The nails and hairs are special horny outgrowths of folds 
in the epidermis. Only primates (monkeys, apes, and man) 
have flat nails, although other mammals have claws, hoofs, or 
horns which are similar products of the skin. Hair is com- 
mon to all mammals, the finer grades, fur and wool, proving 
useful to us in supplying our own relative lack. Like other 
mammals, we too develop a complete coat of hair, but this is 
shed from our bodies during the last month before birth. 



Types of Epithelial Cells 

Plain Muscle 




$> <& o 
Connective Tissue Cartilage Gland Tissue 

Fig. 94. Various types of tissues. (From Buchanan's Elements of Biology. 
Courtesy of Harper & Brothers) 

Hairs grow from columnar follicles in the skin. Each follicle 
has a little muscle attached to it, capable of erecting it (or, in 
our naked poverty, of making goose pimples). There is a 
nerve wound around each one, too, so that any movement of 
the hair can be perceived as a sensation of contact. Each 
follicle also has a side pouch of gland cells which secrete an 
oil that keeps the hair from becoming brittle and lubricates 
the skin. 

The sweat glands, another feature limited to mammals, are 
also pockets of epidermis pushed deep into the dermis. Here 
the secretory cells are in close contact with capillaries, from 
which they filter off water carrying a small amount of dis- 
solved salts. Their rate of secretion is controlled by the auto- 


nomic nervous system, or by adrenalin. The regulation of 
the evaporation of perspiration is one of the principal means 
by which we maintain our body temperature constant and so 
are able ultimately to control our activity regardless of sea- 
son, climate, or weather. 

The mammary, or milk, glands are also specializations of 
the epidermis. In fact they probably are modified sweat 
glands, for in the lower mammals they have the same struc- 
ture as certain large specialized sweat glands. At six weeks a 
"milk line" or ridge appears along each side of the body be- 
tween the front and rear limb buds. Soon all but the anterior 
one third of this disappears, although in various other mam- 
mals paired glands arise the entire length of the lines, and 
even in man there are sometimes extra pairs. The nipples 
are formed shortly before, or even after, birth. 

The deeper layer of the skin is formed from mesoderm; it 
is the dermis. Richly supplied with nerves and blood vessels, 
it is the seat of skin sensation. Its abundance of connective 
tissue makes the skin elastic and flexible, while other cells 
store up fat in a layer that is good insulation against heat 
and cold. 

The muscles 

Muscle cells specialize in movement. We have three types, 
all of which come from the mesoderm. Some muscles are 
made of spindle-shaped cells fastened to one another in 
sheets (see Fig. 94). The peristaltic and constrictive move- 
ments of the stomach and intestines in controlling the passage 
of food through the digestive tube, the constriction of the 
urinary bladder in voiding urine and of the uterus in men- 
struation and labor, and the constriction of the blood vessels 
that regulates the amount of blood flow to each part of the 
body, are movements of these muscles. They cannot be con- 
trolled by the will, as a rule, and are therefore called invol- 
untary. (This is the most primitive kind of muscle cell, for 
it is the only sort found in worms. Striped muscle cells are 


found only on the more advanced level of the crustaceans 
and insects, as well as among the chordates.) 

Heart muscles consist of muscle cells which have numerous 
interconnections, which make them almost one great contin- 
uous muscle cell. They have a spontaneous tendency to con- 
tract rhythmically, even when removed from nervous stimu- 
lation, as when growing isolated in a tissue-culture. Although 
involuntary, they show crossbands, so that they are inter- 
mediate in character between primitive "smooth" muscle and 
the voluntary muscles. 

The muscle fibers of the voluntary muscles are banded 
with cross-stripes. Each fiber is really a composite of a num- 
ber of cells, the nuclei of which are studded over the surface 
of the fiber (see Fig. 94). Like all muscle cells, when such a 
fiber contracts it thickens and shortens; its volume does not 
actually change very much. 

The voluntary muscles of the trunk come from the original 
paired segments of the mesoderm, which quite early fuse 
together until nearly all trace of the segmentation is gone, 
and later, in quite a variety of ways, keep changing direction, 
splitting and fusing, degenerating and even migrating, until 
the muscles are produced. Extending up the back of the 
neck to the skull, these segments supply even the eye muscles. 
But the muscles of throat, face, and jaws come from the gill 
muscles. The facial muscles which are responsible for our 
expressions of emotion are paralleled in other mammals by 
numerous superficial skin muscles which can twitch the skin 
over the whole body. 

The limb muscles make up the bulk of our arms and legs 
and, in addition, form a considerable amount of the over- 
lying parts of chest, back, and loins. The limb buds first 
appear toward the end of the fifth week of development, the 
upper ones slightly in advance of the lower. Into these buds, 
one pair on a level with the heart, the other just in front 
of the tail, there migrate unspecialized mesodermal cells. The 
outer ends flatten into little paddles, constricted off from 



the basal portions, and five lobes appear on each of them. 
By the end of the eighth week, these are molded into recog- 
nizable fingers or toes, and the divisions of the limbs are 
clear-cut (Fig. 95). 

Within the developing bud, the mesodermal cells com- 
mence to specialize, central ones becoming cartilage cells 

Fig. 95. Stages in the development of the limbs between the fifth and eighth 
weeks (magnified about 5 diameters). Upper row, hand and arm. Lower row, 
foot and leg. (From Arey's Developmental Anatomy. Courtesy of W. B. 
Saunders Company) 

and forming a core of cartilage, those around this core becom- 
ing muscle cells. The muscle fibers are bound together in 
bundles by developing sheaths of connective tissue, and at 
the ends of each muscle these sheaths are fastened firmly, 
as tough tendons, to the skeletal structures which are now 
becoming bony. Nerves, too, grow down into the limb, then 
branch, and connect with each fiber. By ten weeks, the first 
feeble movements are beginning, and thereafter a new ele- 
ment enters into the development of the muscles. No longer 
purely automatic, gene- and enzyme-controlled, growth and 
development are from this time on modified by use. Practice 
stimulates development along lines of use, and movements 
become not only more powerful but less clumsy, more deli- 
cately controlled. 

The muscles of the limbs are in two sets, which work in 
opposition to each other. This is necessary, since a muscle 


can do work only by pulling while it is contracting, and 
accordingly a different set of muscles must be supplied for 
counteraction. All of these muscles are located at least one 
joint closer to the body than the part they move. This ar- 
rangement is demonstrably more efficient than a more distal 
one would be. The muscles which move the whole arm 
at the shoulder are thus on chest and back, and those 
which move the leg at the hip are similarly on the trunk. 
These develop first, then those of upper arm and thigh, next 
those of forearm and calf, and finally those in the hand and 
foot. Development regularly moves from center to extremi- 
ties just as it does from the head toward the tail. 

The skeleton 

Most of us think of the skeleton as of use purely in pro- 
tection and support. These functions, to be sure, are im- 
portant, but support itself is only an adjunct to movement. 
The primary function of the skeleton is the part it plays in 
movement. The voluntary muscles produce movements by 
pulling bones into varying positions at their joints. This 
makes necessary firm connections between the bones. These 
connections are provided by ligaments, tough strands of 
white connective tissue (see Fig. 94). The joints, too, must 
work smoothly, without friction. The ends of the bones at a 
freely movable joint are covered with cartilage, the ligaments 
form a sack completely enclosing the joint, and fluid within 
this sack acts as a lubricant, keeping the cartilage soft and 


The skeleton of the head and trunk (axial skeleton) cen- 
ters around the backbone. This begins as a clumping of 
mesodermal cells around the notochord. Each of these se- 
cretes a clear, translucent product, cartilage, around itself, 
a stuff elastic and smooth but not very rigid (see Fig. 94). 
Later specialization (after the seventh week) results in bone 
cells (see Fig. 94). These produce elastic fibers like less spe- 
cialized connective tissues, but they go further by depositing 


around the fibers salts of calcium, mostly carbonate-phosphate. 
This mixture provides great strength and rigidity, while 
cartilage is maintained where flexibility is more essential. In 
each segment the bone cells crowd in and supplant the 
cartilage around the notochord, leaving a pad of cartilage be- 
tween every two blocks of bone, or vertebrae. From each 
vertebra there grows up an arch completely roofing over the 
spinal cord and protecting it. The adjacent muscles of the 
back become attached to a spine projecting from this arch, as 
well as to the body of the vertebra. Projections from the 
vertebra on each side form bases for the ribs, while a couple 
sticking out in front and a second pair behind make articula- 
tions with the vertebrae fore and aft. 

The vertebrae do not all become exactly alike. Those in 
the neck stay relatively small, but grow huge spines for the 
attachment of the neck muscles which move the head and the 
back muscles which move the neck. The two at the very top 
are modified into a kind of ring and pivot joint for firmly 
supporting the skull and yet permitting the head to move 
freely. The thoracic (chest) vertebrae alone carry typical 
ribs in man, although in other animals these extend much 
farther down the spinal column. Five vertebrae in the pelvis 
become fused together to form a firm support for the bony 
girdle to which the legs are attached (this is the sacrum). 
And below that are the three or four remnants of our tail — 
the coccyx. 

One should notice, too, the curves of our backbone (Fig. 96). 
The upper one corresponds to the arch of the spinal column 
which, in horizontal quadrupeds, enables it better to support 
the weight of the trunk suspended from it. But the reverse 
curve, in the region of the loins, or lumbar region, is a 
specialty of man. Without it we could not stand upright, as 
the upper curve would throw our center of balance too far 
forward. This is why the anthropoid apes must stoop— they 
lack a reverse curve which would bring their center of grav- 

3 o8 


Fig. 96. Spinal curvatures at various ages, viewed from the right side. (From 
Arey's Developmental Anatomy, after Peters. Courtesy of W. B. Saunders 

ity back over their hips. Now these curves are not present 
even at birth, the backbone being still in the form of a sim- 
ple arch. The weight of the body and the pull of muscles as 
an erect position is finally assumed are thought to be neces- 
sary to bring them out. 

The skull is formed of many bones which gradually fuse 
together. The cranium, that part which encases the brain, is 
not all cartilage to begin with. While the back, base, and 
temples are first present as cartilage that is later transformed 
into bone, the bones that cover top and forehead are formed 
in the membranes that cover the brain (Fig. 97^). They 
gradually spread out until they meet, but even in the infant 
there are still "soft spots," parts of the membrane into which 
they have not yet extended. As the bones of the cranium 
lengthen, they meet and interlock like pieces of a jigsaw 
puzzle. Gradually even these seams are obliterated, and in 
an old person the cranium is a single sheet of bone. Thus the 
approximate age of a person at death can be read from his 

To the cranium are fastened the facial bones which either 
begin as capsules of cartilage enclosing the inner ear and 



Fig. 97. A, the bony skeleton at birth. (From Arey's Developmental Anat- 
omy, after Scammon and Hess. Courtesy of W. B. Saunders Co.) B, the 
skeletal derivatives of the gill arches. (From Goldschmidt's Ascaris. Courtesy 
of Prentice-Hall, Inc.) 

Lower Jaw 

Bonu Ring of 

Second Gill Arch 

-Third Gill Arch 

"YThird and Fourth 
Gill Arches 




olfactory (smelling) organs, or form from membranes-the 
cheek bones, the bridge of the nose, and most of the eye- 
socket. Parts of the nasal cartilages, of course, never turn to 

Other skeletal parts of head and neck come from parts of 
the cartilaginous gill bars (Fig. 97B). The first pair of these 
is covered over and replaced by bones from the skin, making 
a right and left upper and lower jawbone. The bony replace- 
ments form a new jaw joint in front of the ear, and the old 
joint, as we have seen, is cut off and left to transmit sound 
across the middle ear. The jawbones grow forward until they 
meet and fuse in front. (That is, they do normally. Mutant 
genes responsible for failure here are variable in expression, 
resulting in cleft chin, cleft palate, or harelip. These defects 
may be fatal or, when mild, merely disfiguring.) The bony 
palate similarly appears as two flat pieces of bone that grow 
across from the upper jaws until they meet, separating the 
nasal cavity from the mouth in front but leaving them con- 
nected farther back. 

As we have already observed, the upper end of the second 
cartilaginous gill bar develops into the stirrup, the third of 
the bridge of little bones across the middle ear. The lower 
part of the bar also becomes bone, a part of the hyoid bone 
which supports the base of the tongue. The rest of this bone 
comes from the third pair of gill bars. The fourth and fifth 
pairs remain cartilage, and are expanded and modified into 
the cartilages of the larynx, to which the vocal cords are at- 
tached. On the whole, then, a number of parts of the gill 
bars find some later use, but other parts are formed only to 

The ribs grow out from the vertebrae, become cartilage, 
then bone. Those in the neck are very short and are fused 
with the vertebrae. Then come the twelve pairs of regular 
ribs, curving around the chest. The front portions of these 
where they connect with the breastbone, remain cartilagi- 


nous, and the breastbone (or sternum) is itself not completely 
transformed to bone. The two lower pairs of ribs never be- 
come attached and remain "floating" in front. The next 
group of vertebrae have short ribs fused into them, while the 
fused vertebrae that make up the sacrum (Fig. 98) have fused 
rib projections which help to make an adequate support for 
the rest of the pelvis. 




Fig. 98. An early stage in the development of the sacrum and coccyx. The 
ribs appear only on the four sacral vertebrae. 

The limbs are fastened to two girdles, the shoulder girdle 
and the pelvis. We should note that in all the higher ani- 
mals, from certain fossil lobe-finned fishes on up the scale 
through amphibians and reptiles to birds and mammals, the 
limbs and their girdles are built on the same plan. Bone for 
bone they correspond, with only minor modifications in size 
and shape or number of digits. The fins of lobe-finned fish, 
the legs of a frog or lizard, the wings and legs of a bird, the 
paddles of a whale or the flippers of a seal, and our own arms 
and hands, legs and feet, are homologous structures, although 
adapted to various uses. This must surely mean that the 
primary genes concerned with the nature of limb develop- 
ment are the same in all the members of this group, although 
secondary genes have become different through mutation. 

The pelvis, bony girdle to which our legs are attached, is 


rigidly fixed to the sacrum, but our arms are fixed to a 
shoulder girdle resembling those of other mammals whose 
forelegs must take the full impact of their body weight in 
running and landing after a leap. The great bone of the 
upper arm, the humerus, is attached most indirectly to the 
backbone. Its ball fits into a socket joint which allows the 
arm to move freely in all directions at the shoulder. This 
socket is provided by the shoulder blade (scapula), the large 
flat body of which lies imbedded between the shoulder and 
back muscles, which take up much of the shock of landing. 
Close to the shoulder joint, the shoulder blade is braced by 
a curving collarbone (clavicle), which is attached at its other 
end to the top of the sternum (breastbone). Among mam- 
mals the collarbone is well developed chiefly in those that 
climb, dig, or fly, while in running quadrupeds it is vestigial 
and the whole shoulder girdle is "floating." The two collar- 
bones serve to brace the shoulder joints and allow consider- 
ably greater freedom of arm movement, but they are not 
strong enough to withstand the full shock of landing on the 
forelimbs, and are frequently broken. The sternum is con- 
nected with the ribs only by flexible cartilage, and the ribs 
themselves are shaped to serve as springs. Thus a mere frac- 
tion of the jar of landing reaches the backbone and is trans- 
mitted to the body as a whole. How different when we jump 
and land on our feet! Only a bit of the shock can be taken 
up by bent knees, and the rest of the force of impact sends 
tremors through our whole frame. It is impossible for us 
really to "land lightly on our feet." So far as our limb girdles 
are concerned, we are undeniably constructed to leap and 
land on all fours, but the rest of our anatomy fails to corre- 
spond. It has been modified to make possible an upright 
carriage, while the flexible attachment of the forelimbs, cer- 
tainly no disadvantage to us, has been retained. (The front 
tip of the shoulder blade represents a vestige of a third bone 
— coracoid— of the shoulder girdle, present in other verte- 
brates. Like the collarbone, it braces the shoulder, coimect- 


ing with the lower end of the sternum. In our development, 
it gets only as far as a ligament, with a few bits of cartilage 
imbedded here and there along it. This has decreased the 
strength of the shoulder joint; but as we no longer practice 
landing on our forelimbs, it does not matter.) 

At the elbow are two interesting joints. There are two 
bones in the forearm, the radius and the ulna, the latter on 
the same side as the thumb. A prong of the ulna slides in a 
groove in the humerus, making a hinge joint which acts as 
a final check on the movement produced by the triceps mus- 
cle when the forearm is extended. The radius has a flat disk- 
like upper end which pivots on the humerus, thus en- 
abling us to turn our hands over. The two types of motion 
represented here emphasize the relation of joints to move- 

These long bones, together with those of the leg, are hol- 
low in the shaft and spongy at the ends. This is the con- 
struction which, on engineering principles, is by far the 
strongest for a given mass and is for that reason used ex- 
tensively in making tubular metal furniture. The cavity of 
the long bones is not waste space, however. The shaft is filled 
with yellow marrow, a store of fatty substances, and the cavities 
of the spongy bone contain red marrow, whence come the red 
blood corpuscles and other blood cells. The bone itself is 
not solid. Under the microscope, sections show many fine 
canals through which blood vessels and nerves make their 
way to still smaller cavities where dwell the single bone cells, 
imprisoned by their own product, and communicating with 
one another only by delicate projections. But this is so only 
in a fairly mature bone. Like most other parts of the skele- 
ton, the long bones start out as clumps of mesodermal cells 
which turn to cartilage. After this has assumed the rough 
shape of the bone, centers of bone formation arise in and 
around it. As mineral matter is deposited, the cartilage is 
gradually surrounded by a shaft of bone, while within the 
cartilage itself spongy bone is formed. The cartilage degen- 



erates, and along with it some of the spongy bone, and thus 
the marrow cavities are created (Fig. ggE, F.). 

Growth must take place without interfering with the ac- 
tion of the joints. At first, bone cells replace the cartilage 
only in the shaft, and the ends are still formed of rapidly 
growing and readily modifiable cartilage (Fig. 99^ -C). Later, 

Fig. 99. Stages in the growth of a long bone. A, cartilage. B, C, spongy bone 
(stippled) being deposited within the cartilage and compact bone (black) 
being deposited around it. D, epiphyses appearing at each end of the bone. 
E, the marrow cavity (sparse stipple) appearing through degeneration within 
the spongy bone. F, epiphyses finally uniting with the shaft, leaving articular 
cartilage at each end. The marrow cavity is continuing to enlarge as more 
bone is deposited on the outside of the shaft. (From Arey's Developmental 
Anatomy. Courtesy of W. B. Saunders Company) 

centers of bone formation appear also in the ends of the 
bones (Fig. 99D). Growth in the length of the bone there- 
after takes place between these epiphyses, as they are called, 
and the shaft through a formation of new cartilage which is 
gradually transformed into bone. Most of the epiphyses do 
not appear until after birth, and many not until adolescence. 
During all this time, when shaft and ends are finally being 
fused, the calcium supply in the diet is a matter of great im- 
portance. At maturity, the shaft and ends are finally fused, 
and the bone stops growing in length. Growth in diameter 
of either the shaft or the ends is no problem— more bone is 
simply added on as a superficial layer, while the central 


marrow cavity becomes enlarged by resorption of bone from 

The pelvis is a complete ring of bone, except in front, 
where a small gap is closed by cartilage and ligaments. 
These provide some elasticity, which is especially important 
in childbirth. During labor, the babe must pass from its 
mother's uterus down through the vagina. This opens below 
the pelvic ring, and birth would be extremely difficult or 
even impossible if previous preparation had not been made. 
Some influence, perhaps a hormone, causes the ligaments here 
to relax during the birth process, allowing the pelvis to open 
up more broadly. 

The leg bones, femur in the thigh, tibia and fibula in the 
shank, are similar to those in the arms, except that the fibula 
no longer pivots at the knee, but becomes fused to the tibia 
(shin bone) below the knee joint. Hence the knee is only a 
hinge joint. It is protected by the kneecap, a little floating 
bone formed within a muscle tendon. 

The direction of the knee joint is, however, the reverse of 
that of the elbow. This again is interpretable in terms of the 
structure of other vertebrates. Primitive land animals had 
spraddled legs, with both elbow and knee directed outward. 
With increasing length of limb, the legs were drawn under 
the body where they supported it more effectively, so that 
the muscles were relieved of considerable work. This devel- 
opment involved rotation of the limbs, rotation which took 
place in opposite directions, the elbow facing backward, the 
knee forward. Although we as men no longer creep, crawl, 
or run on all fours, the rotation of our limbs indicates the 
ancestral condition, still retained by most mammals. 

Concerning wrists and ankles, hands and feet, toes and fin- 
gers, volumes could be (and have been) written. 9 The won- 
derful flexibility of the hand, with its opposable thumb, as 

9 See especially the fine exposition by Sir Charles Bell, the noted nineteenth- 
century surgeon, on The Hand. This pre-Darwinian volume of the "Bridge- 
water Treatises," written to illustrate the power, wisdom, and goodness of 
God, is a great classic of anatomy. 


controlled by our brain, has been an important, perhaps even 
an essential, factor in our upward rise from savagery. Yet the 
monkeys and apes are better equipped in this respect than 
we, for they are four-handed. The use we make of our hands 
is evidently even more a matter of the intelligence that con- 
trols them than of their own inherent powers. It is really in 
the feet that we are unique. Bone for bone and muscle for 
muscle, the structure of the human foot corresponds to that 
of the lower "hand" of an ape. Yet our greatly shortened 
toes and relatively huge big toe on the inside have been 
drawn into line, and the big toe has lost most of its opposa- 
bility. Together with the big heel bone that now touches the 
ground and the increased arch and rigidity of the instep, 
these are modifications of the primate "hand" that have 
made possible our erect carriage and have freed our own 
hands for manipulation. 


The appropriateness of our responses depends upon the 
existence of pathways for transmitting impulses from the ex- 
cited sense organ to the muscle or gland cells which are our 
means of response. These pathways, potentially connecting 
every sense organ with every muscle and gland cell, are pro- 
vided by the cells of the nervous system. 

We have seen how this originates, very early in our devel- 
opment, as a hollow tube along the back, made from a fold- 
ing-in of the outer layer, the ectoderm. As this tube grows, 
its walls thicken considerably, and the central cavity becomes 
proportionately smaller and smaller, although even in the 
mature spinal cord and brain we can find vestiges of it. At 
intervals corresponding to the muscle segments, nerves grow 
out in pairs from the cord, lengthen toward the sides of the 
body, extend into organs, body muscles, limbs, or skin, 
branching as they go, until eventually every sense organ, 


gland, and muscle is supplied with nervous connections. 
What are these ' 'nerves"? 

If we cut a nerve and examine it under high magnifica- 
tion, it appears to be made like a cable. It is a bundle of a 
great many fibers, most of them covered with a whitish insulat- 
ing sheath of connective tissue, the whole bundle being held 
together by a similar sheath. These nerve fibers are sorted out, 
at the branchings of the nerve, to their separate destinations. 
If we follow the course of these long fibers, we shall find 
that they are very long, fine extensions of the cytoplasm of 
nerve cells. Those which extend to a sense organ usually 
end in a brushlike tuft of little branches, while the ones 
which pass to muscle fibers end in a plate on the side of the 
muscle fiber. 

The sensory nerve fibers grow out from cells which lie in 
little clumps, known as ganglia, alongside the spinal cord. 
Each fiber branches in or near the ganglion from which it 
arises; and if we follow the other fork, we can trace it into 
the dorsal side of the spinal cord, where it forks into several 
branches, most of which pass up toward the brain, but some 
of which grow down the spinal cord to lower levels. Some of 
these cells in man attain a length of more than five feet! 
Each branch ends in a tuft of microscopic branchlets which 
make contact with other nerve cells. 

Other fibers in each nerve are motor nerve fibers, their 
impulses stimulating the muscle fibers to contract. These 
motor nerve fibers come all the way from cells in the spinal 
cord. The cells themselves are irregular, for they have num- 
bers of short tuftlike projections (dendrites). Between the 
ends of the sensory and motor nerve cells in the spinal cord 
a third kind of nerve cell, known as an association nerve cell, 
makes connection. In this way an excitation of the sensory 
ending, by a pinprick on the finger, for example, will lead to 
transmission of an impulse along the sensory nerve fiber to 
the association nerve cell, and thence to the motor nerve 
cell, over whose fiber it will reach the muscle fiber, stimulat- 



ing it to contract and withdraw the finger. This simplest 
type of hookup, in which the response is completely auto- 
matic, is known as a reflex arc. Never is nervous action as 
simple as this in reality— certainly not in the present ex- 
ample. The impulse from the sensory nerve cell will actually 
be passed to several association nerve cells, some, like the one 

Nerve Cells 

Motor Tract 
(from. Brain) 



Sensory Tract (to Brain) 
/ s~— Receptor 





Fig. 100. Diagrammatic sketch of a segment of the human spinal cord, show- 
ing nervous pathways and connections. (Redrawn from Buchanan's Elements 
of Biology, after Kuhn. Courtesy of Harper & Brothers) 

shown in Fig. 100, passing the impulse on to motor nerve 
cells, with the result that the response is a coordinated con- 
traction of a number of muscle fibers; others passing the im- 
pulse on up the spinal cord to various parts of the brain, 
where numberless complications may be involved in our 
further responses, such as saying "Ouch," or kicking our tor- 
mentor, or plotting some deeper revenge. 

The synapse 

A very important feature of nervous transmission is the 
nature of the contact between the fibers of different nerve 
cells. This contact is known as a synapse. 


A very significant thing about synapses is that, unlike nerve 
fibers, they will transmit an impulse in only one direction. 
Upon this characteristic depends the chainlike nature of the 
paths taken by impulses through the nervous system. Here is 
the basis for the perception of sequence within us-perhaps 
we are able to perceive time only because our nervous system 
is thus channelized. It is fascinating to speculate whether our 
boasted logic is an outgrowth of this-and we wonder vainly 
what the timeless existence of a Hydra, whose nerve net 
transmits in all directions, must be like. 

In the second place, the synapse appears to be improved 
by use in its capacity to transmit a nervous impulse. Let us 
get a clear picture of all that this implies, for it is very likely 
the basis of our ability to learn. Through the nature of our 
hereditary pattern acting during development, we are pro- 
vided with billions of nerve cells in spinal cord and brain, 
with a veritable wilderness of ready-made and potential con- 
nections. The ready-made ones provide us with a basis of 
unlearned behavior patterns which we call reflexes and, when 
more complex, instincts. It is true that man has very few of 
these ready-made behavior patterns in comparison with in- 
sects, for example, in which they predominate, for even our 
so-called "reflexes" are to a considerable extent developed by 
prenatal use and practice. Consequently, the mental wilder- 
ness is largely trackless, except as we make paths through it. 
Our first efforts to adjust ourselves are blind— excellent exam- 
ples of trial and error. But somehow, whenever by mere chance 
a response is tried which turns out to be effective, the synapses 
along the pathway which lead to it are improved. As we ac- 
cumulate experience, pathways are beaten down into "high- 
ways" along which nerve impulses are guided effortlessly, 
and we achieve a habit. This explains, too, why it is so hard 
to break a habit. It is as though nerve impulses, like men or 
cattle, resist being diverted from their accustomed route to 
one less easy. 


The spinal cord 

The spinal cord is the great trunk route for nerve fibers 
ascending to the brain or descending from it, besides provid- 
ing numerous local connections. The cell bodies become ar- 
ranged centrally, appearing in the form of a gray letter H in 
a cross section of the cord, with the white-coated ascending 
and descending fibers around the outside. Because the sen- 
sory nerve cells are outside the cord, in ganglia, the dorsal 
horns of the gray matter remain more slender than the 
ventral ones, which contain the large motor nerve cell bodies. 

Most of the nerve fibers in the white matter cross over 
somewhere on their way up or down the spinal cord, and so 
the right side of the brain receives impulses from, and sends 
them to, the left side of the body, and vice versa. Nerve 
fibers of similar function occupy definite columns of the 
white matter, with the more local relays clustered mainly 
next to the central gray matter. 

The fore brain 

The brain, as we have seen, first shows up as a series of 
three bulging vesicles at the front end of the neural tube. As 
development proceeds (see Fig. 101), this original portion is 
so covered over and surrounded by new parts that it may be 
hard to discern, but it still forms the vital brain stem con- 
necting all the major parts which have grown out from it. 

In the sixth week of development the forebrain pushes 
forward two pouches, in front of the points of origin of the 
stalks which form the optic cups. These pouches grow forward, 
upward, outward, and finally backward, expanding until the 
brain stem is completely concealed by them. They are the two 
cerebral hemispheres, or cerebrum. Their enormous growth 
and development constitute the major difference between our 
brain and the brains of other vertebrates. In fish and reptiles 
they are small and are concerned entirely with the sense of 
smell. In reptiles a new area of growth occurs that becomes 



Forebram-^ ^-Midbrain 

Eye — -~^ \^~~^Z ^Hindbraia 

. ' / > ^InnerEar 






W^W a } Heart' „ 


\ Thalamus 





Hemisphere / { 





Out line of 






Fig. 101. Stages in the development of the human brain. A, at about three 
and one-half weeks. B, at nearly four weeks. C, at five weeks. D, at seven 
weeks. E, at three months. (Redrawn with modifications from Arey's Devel- 
opmental Anatomy, after Patten. Courtesy of W. B. Saunders Company) 

devoted to higher mental activities, such as the formation of 
associations and learning. It is this area which becomes pro- 
gressively larger in birds and mammals, until it completely 



overlies the original "smell-brain" and reaches its culmina- 
tion in man. 

The cerebral hemispheres have a layer of gray matter 
(nerve cells) on the surface, and the internal portion is com- 
posed of white matter. This reversal of the relative situa- 
tions of gray and white matter in the spinal cord represents 
a new arrangement better suited to an enormous develop- 
ment of the gray matter. The surface area also becomes 
folded (only slightly in many lower mammals) into elaborate 
grooves and wrinkles in our own brain, thus supplying addi- 
tional room for the nine billion nerve cells concerned with 
these newer activities of the brain. The functions of a num- 
ber of the areas bounded by these grooves have been mapped. 
In the lobe just behind the ear lies the center for hearing 
and speech, at the rear is one for vision, and on either side of 
a prominent groove running from the top of each hemisphere 
down to the temples are parallel motor and sensory areas, 
from toes at the top to lips at the bottom. Other motor func- 
tions are to be found in the frontal lobes, but most of these 
and great areas of the posterior part cannot be assigned 
definitely. They are commonly thought to be the seat of the 
highest mental functions of all, for this is where we differ 
most from our closest relatives, the apes. These are known as 
association areas. 

If we split the mature brain lengthwise (Fig. 102), a strik- 
ing band of white matter at once catches our attention. It is 
the corpus callosum, a tract of nerve fibers which connects 
the two hemispheres. Just beneath this is a rounded body, 
the thalamus, connected by dense strands of fibers with the 
great internal reflex and distributing mass (corpus striatum) 
of each cerebral hemisphere. The thalamus is the final stage 
of the original forebrain, and is an extremely important re- 
gion. All the ascending and descending fibers from the 
cerebral hemisphere pass through it; the automatic internal 
activities have here their ultimate coordination and control; 
it is the center of reflexes connected with smell and taste; pain, 





— Corpus 
Call 05 urn 


Cerebellum - 2 

Medulla — — 


Posterior Lobe 

of the 
Pituitary Gland 

, -Pons 


Fig. 102. Median longitudinal section through the mature human brain. 
(Redrawn with modifications from Plunkett's Elements of Modern Biology. 
Courtesy of Henry Holt and Company) 

pleasure, and simple emotions are felt here; and tempera- 
ture and the interplay of the endocrine glands are regulated 
in this region. Often, in considering the brain, the functions 
of the cerebral hemispheres alone are emphasized. We will 
do well not to forget that below these lies the brain stem, 
inconspicuous but essential. As C. J. Herrick says, "When- 
ever elementary emotions ... are complicated by interpreta- 
tions, are elaborated through association with other kinds of 
experience into sentiments, sympathies, aversions, jealousies, 
and the like, or are deliberately joined with impulse in vol- 
untary action, then thalamus and cortex are working in part- 
nership. The thalamus supplies the emotional coloring, the 
agreeable or disagreeable quality, and the simple impulsive 
drives; the cortex supplies the intelligent guidance and ra- 
tional control. The thalamus, then, discharges two ways, 
downward toward the motor centers and upward toward the 
cerebral cortex. The former regulates and reinforces our ele- 
mentary visceral reactions and is one of the most primitive 
functions of the brain. The latter links these reactions and 



the accompanying emotions with the higher centers of intel- 
ligent control and keeps them in hand in the more restrained 
life demanded by good society." 10 The thalamus thus pro- 
vides a goodly share of the behavior patterns that make up 
our personality! 

The midbrain 

This part of the brain stem, which in fishes is the most 
prominent region, remains relatively undeveloped in human 
beings. There are four little hillocks just behind the thala- 
mus, and a floor through which the ascending and descend- 
ing nerve fibers pass from thalamus to hindbrain. Yet there 
is something very interesting about these four hillocks, for 
to the first pair are distributed nerve fibers from the eyes, 
which have crossed and entered the brain below the thala- 
mus, just in front. 

The nerve fibers from the left and right sides of each eye 
are sorted out together at this crossing, so that the two images 
of each object, seen by each eye from a slightly different 
angle, are made to coincide through distribution to the same 
part of the brain. In this way we acquire stereoscopic vision 
and a finer judgment of distance, a gift only the monkeys and 
apes share with us. These first two little hillocks of the mid- 
brain, to which some of the optic nerve fibers pass, still re- 
main our center for visual reflexes, and this whole part of the 
brain in lower vertebrates is concerned with vision. 

The second pair of little hillocks is a similar center for 
hearing reflexes, such as "pricking up the ears." How is 
it that we, who depend heavily upon sight and hearing 
as our avenues of information, boast the greatest develop- 
ment ever attained by that part of the brain originally con- 
cerned with smell, and have such insignificant "sight-" and 
"hearing-brains"? Those genes which, by mutation in our 
ancestors, led to the progressive development of our cerebral 

10 The Thinking Machine, ed. 2, p. 118. University of Chicago Press, 1932. 


hemispheres must have been superimposed on the hereditary 
pattern of a mammal that, like most other mammals today, de- 
pended primarily on his sense of smell and had a relatively 
large "smell-brain." 

With an increased predominance of the sense of smell, 
those centers in the forebrain which correlate smell with vis- 
ual, auditory, and other sensations, and with motor activities, 
became tremendously developed. In short, practically the en- 
tire interpretation of these sensations and the voluntary con- 
trol of the muscles and glands was transferred to the various 
areas of the cerebrum, leaving only reflex control in the 
original centers. Many of the sensory fibers from the eyes 
and ears were even "short-circuited" to the correlating cen- 
ters of the cerebrum, so that now we "see" and "hear" in 
these centers rather than in the midbrain. 

The hindbrain 

The hindbrain comprises three main structures. Two, the 
pons and medulla, constitute the hind portion of the brain 
stem, which consists in large part of nerve fibers which con- 
tinue on into the spinal cord and in the other direction pass 
to midbrain, thalamus, and cerebral hemispheres. Many of 
these, too, terminate in this region, for from it emerge all of 
the twelve pairs of cranial nerves except the first four. (Two 
of these first four, the olfactory and optic "nerves," are purely 
sensory— smell and vision— projections of the forebrain; the 
third and fourth are motor, controlling some of the muscles 
that move the eyeball.) The eight pairs of nerves of the 
hindbrain include motor nerve fibers for the eyeball, jaw and 
face, pharynx, tongue, salivary and tear glands, neck, and 
even such lower organs as trachea, esophagus, stomach and 
small intestine, liver and pancreas, and diaphragm and heart; 
they also include sensory nerve fibers from most of these parts 
and, in addition, the very important auditory nerves from 
the ears. Such a number of important nerves evidently re- 


quire numerous associations in the part of the brain they 
enter; consequently the pons and medulla are great reflex and 
relay centers. Here the rate of respiration and of heartbeat, 
and the determination of the amount of blood flow to par- 
ticular parts of the body, swallowing, vomiting, coughing, 
and sneezing are all regulated. 

The cerebellum grows out from the roof of the hindbrain 
close to the midbrain. Like the cerebrum, the cerebellum 
has its cells (gray matter) on the outside, with the nerve 
fibers forming a white treelike structure in the interior. 
Fibers connecting its right and left lobes with the cerebrum 
cross underneath the brain stem, forming the conspicuous 
ventral part of the pons. 

The sensory nerve fibers from the part of the ear which is 
concerned with balance, position, and movement in space 
enter the pons and are relayed to the cerebellum, which is 
the great reflex center for muscle coordination. Practically 
all the voluntary muscles are involved in maintaining our 
equilibrium, and this part of the brain therefore becomes a 
center for their coordination even in voluntary movements, 
although the original impulses may come from the cerebral 

The autonomic system 

We have thus far overlooked one very important part of 
our nervous mechanism. There are two additional chains of 
ganglia, a pair to each body segment, which parallel the 
spinal cord. These are the sympathetic trunks of the auto- 
nomic system. Apparently they are formed by the migration 
of individual cells from the neural crest, a strip of ectodermal 
cells left along the back, between the outer ectoderm and the 
neural tube, when the latter is closed over. They journey 
down the dorsal (sensory) nerve roots, some of them stopping 
on the way to form the spinal ganglia. Other cells migrate 
out from the spinal cord along the ventral (motor) nerve 
roots. When the migratory cells reach the correct spots (we 


may well wonder how they recognize them), they form clus- 
ters and send out nerve fibers to connect with adjacent 
ganglia until the chains are formed. They also send out 
nerve fibers to the internal organs, governing their automatic 
activities. Our solar plexus is a cluster of nerve fibers and 
ganglia belonging to this system, and we have all experienced 
how a blow over it "knocks the breath out of us" by par- 
alyzing, among other things, the nerve supply to the dia- 

The terminal nerve cells of the sympathetic ganglia liber- 
ate sympathin. This is a substance which has a powerful 
stimulating effect upon the organs innervated. But a regula- 
tion limited to stimulation and nothing else would be most 
ineffective. The control of the autonomic system over the 
internal organs is based on antagonistic action. Besides the 
sympathetic portion, there is a parasympathetic portion that 
innervates the majority of the same internal organs. The 
terminal nerve cells of the parasympathetic ganglia liberate 
acetylcholine, a substance which strongly inhibits the activ- 
ities of the organs innervated. The sympathetic portion of 
the autonomic system is connected with the spinal nerves of 
the thoracic and lumbar regions; the parasympathetic trunks 
arise partly from the hindbrain and partly from the sacral 
region of the spinal cord. 

The autonomic system is connected also with the central 
nervous system by sensory nerve fibers. In every segment 
these pass through the autonomic ganglia to the spinal cord 
by way of the spinal nerves. Accordingly, the internal organs 
are not completely isolated from our brains. Sensations of 
pain may rise from them into our consciousness, and some 
measure of control can be exerted over the organs by the 
medulla and the thalamus. Yet fortunately for us, because 
of their largely reflex system of control, we can go along 
happily oblivious of our inner workings most of the time, 
free from the necessity of attending to them consciously. 



Besides the nervous system, other means of correlating the 
varied activities of the different parts of our complex bodies 
are also provided— chemical means, resembling in their action 
the "organizers" of earlier development. Substances synthe- 
sized in one place pass into the blood, are distributed through 
our whole system, and here and there exert some effect upon 
an organ especially sensitive to them. These substances are 
the hormones, and the organs which produce them are called 
the endocrine, or ductless, glands. They are widely scattered 
in our bodies. 

We have already noticed how the intestine produces se- 
cretin, which sets pancreas and liver to secreting pancreatic 
juice and bile whenever food enters the intestine from the 
stomach. Another hormone, very similar chemically to se- 
cretin, is produced in the same region, and stimulates the 
gall bladder to contract and discharge the bile stored in it 
into the intestine. And, during our survey of the digestive 
system, we have seen how the islet tissue of the pancreas pro- 
duces insulin. 

The parathyroids, products of the third and fourth pairs 
of gill pouches, are other endocrine glands of vital impor- 
tance to us. They regulate the concentration of calcium ions 
in our blood, upon which there depend not only the strength 
and firmness of our bones and the efficiency of our calcium 
metabolism but also the irritability of our muscles. Since 
these tiny glands come to lie on the very surface of the 
thyroid gland, and may even be imbedded in it, an operation 
on the latter for goiter, unless performed with modern pre- 
cautions, may inadvertently cause the removal of the para- 
thyroids too. Then the calcium concentration of the blood 
falls alarmingly, the muscles and nerves become more ir- 
ritable, the muscles begin to twitch, and finally go into con- 


vulsive spasms which end fatally, unless a calcium salt or a 
dose of the hormone is injected into the blood. When a 
tumor of the parathyroids results in excess secretion of their 
hormone, calcium is lost from the bones to the blood, the 
skeleton loses strength, the teeth decay. Thus the parathyroid 
hormone controls, on the one hand, muscle and nerve irrita- 
bility and, on the other hand, the adequate development of 
bones and teeth. 

The thyroid gland 

The hormone of the thyroid gland, thyroxin, 11 is a rela- 
tively simple organic chemical substance, an amino acid con- 
taining iodine. Only very slight amounts are necessary at any 
one time— in fact, the amount normally produced by one in- 
dividual in a whole year (31^ grains) could be put into three 
or four medium-sized gelatin capsules. Yet a deficiency of 
thyroxin during the years of childhood and adolescence is 
sufficient to make one an imbecile, of a type known as a 
cretin. These unfortunates are stunted and deformed in body 
as well as in mind, all for the lack of a tiny bit of a certain 
chemical substance, which, if supplied soon enough, can do 
wonders in restoring to them a relatively normal mind and 
body. What role has thyroxin in our body activities that 
makes it so important? 

The effects of an excess or an insufficiency of it reveal the 
answer. The person with too active a thyroid gland has a 
faster heartbeat and higher temperature than normal. He 
frequently is excitable and irritable, oversensitive and hard 
to get along with. He may suffer from insomnia, and is likely 
to be thin. Finally, if the overactivity of the gland is due to 
its enlarged size, there will be a goiter on the throat, along 
with popeyes. What a contrast in the person who has an 
underactivity of the gland! The action of muscles, glands, 
and circulation is sluggish; body temperature is lower, and 

11 The actual hormone is probably a compound of thyroxin with a protein. 


hands and feet are often cold; there is a tendency to put on 
fat, and the skin is often puffy. The personality, too, suffers, 
for such a one is inclined to be indolent and slow of wit. In 
other words, thyroxin regulates the rate of metabolism, which 
is all-pervading in its influence. 

Another type of goiter results from an effort to compensate 
for a lack of iodine in the diet by an enlargement of the 
thyroid gland. Naturally, this kind of goiter occurs mainly 
in certain regions where iodine is scarce. This is principally 
in glaciated regions where the action of the ice has removed 
the topsoil containing most of the iodine. Switzerland and 
our own Great Lakes region are examples of "goiter belts," 
where in places one fourth of the men and more than 
one half of the women are affected. Use of iodized salt can 
cut this incidence down to nearly zero; for example, among 
Detroit school children it was cut from 35 per cent to 1 per 
cent in eleven years. These goiters develop especially at 
periods when the body activities are highest and the demand 
for thyroxin is accordingly greatest, as before birth, at pub- 
erty, and during pregnancy and nursing. 

The thymus gland 

Developing from the hinder parts of the third and fourth 
gill pouches is a huge gland— the thymus— that is still largely 
a mystery. It is large at birth, begins dwindling in infancy, 
and has usually disappeared completely by puberty. Has it 
something to do with growth, with the attainment of sexual 
maturity, or with the growth of the skeleton and the utiliza- 
tion of calcium? All these are claimed, but none of them is 
known with certainty. At present our chief interest in this 
gland is that its huge size in newborn babies may prevent 
easy breathing, and even suffocate them by pressing on the 
windpipe. Often nowadays babies are x-rayed to see whether 
there is any danger of this, and then, if necessary, are given 
an x-ray treatment that reduces the size of the gland. 


The adrenal glands 

Each of these glands, situated like yellowish caps on the 
top of each kidney, is really two glands, for the inner and 
outer portions have different origins and synthesize entirely 
different hormones. The medulla, or central portion, pro- 
duces adrenalin. Its chemical structure has been worked out, 
and it can be synthesized in the laboratory as successfully as 
in the adrenal glands in the body. It is wonderfully potent, 
minute injections speeding up the heartbeat, raising the 
blood pressure, diverting blood from the skin and internal 
organs to the muscles, at the same time increasing the sugar 
concentration of the blood, raising the resistance to fatigue, 
and speeding up blood clotting. In all of these effects it 
duplicates the action of the sympathetic portion of the auto- 
nomic nervous system, a fact of great interest because the 
medulla of the adrenal glands develops in the embryo from 
special cells migrating out of the solar plexus of the sympa- 
thetic system, and the terminal nerve cells of the sympathetic 
produce sympathin, which acts like adrenalin. 

The effects of adrenalin are those associated with excite- 
ment, anger, fear, and danger, and should be of great help in 
emergencies. Many physiologists believe that adrenalin plays 
such a role, but there is still some doubt whether it actually 
is secreted in extra amount during crises. As to its normal 
role, it has not been conclusively shown to have any. It is 
present in the blood in only one part in 20,000,000, and this 
is too dilute to have any obvious effect. At least removal or 
inhibition of the medullas of the adrenals has no clear-cut 
effect. Read the opinion of textbooks on this point with 
caution, even though it is hard to think of such large and 
active glands and of so potent a hormone as valueless to us. 

The outer portion of the adrenal glands, their cortex, 
grows from the mesoderm. It produces a hormone or several 
as yet unseparated hormones called cortin. This is unques- 
tionably vital, removal of the entire adrenal glands being 


quickly fatal. Cortin is perhaps the means of controlling the 
concentration of the sodium, chloride, and potassium ions in 
the blood, as disease of the adrenalin cortex results in lowering 
the two former and raising the latter. The secretion of the 
adrenal cortex also has marked effects upon sexual develop- 
ment, as will be seen later. 

The pituitary 

In a little hollow in the floor of the cranium, just beneath 
the midbrain, lies the pituitary body, a gland about the size 
of a hazelnut. Its two parts, anterior and posterior, are of 
separate origins, and, like the two parts of the adrenals, may 
be considered essentially different glands. 

Most of the posterior part is a growth from the lower part 
of the thalamus, with which it remains connected by a stalk. 
Substances have been extracted from it which powerfully 
stimulate smooth muscles, especially those of the smaller 
arteries and of the uterus, to contract. This raises the blood 
pressure, steps up the secretion of urine, and causes spasms 
in the uterus, even in a concentration of one part in 15,000,- 
000,000 of blood, so that the extract is a potent drug in the 
hands of a doctor for speeding up delivery at childbirth. 
However, whether or not it is normally secreted at such times 
is uncertain, and we must hesitate to label it definitely as a 
hormone, since removal of this lobe of the pituitary seems to 
have no effect upon blood pressure or labor. 

The anterior lobe of the pituitary is a portion of the 
original pouch from the roof of the mouth (see p. 277). No 
less than five hormones are known to be produced here. 
One of them regulates the growth of the body. Should the 
gland become overactive in producing this hormone, a phe- 
nomenal increase in size will take place. Most of us are 
familiar with circus giants, and have seen news pictures of an 
eight-foot, 400-pound boy, or of a huge one-time heavyweight 
boxing champion of the world. In 1935 there were reports 


of a young Egyptian carpenter who fell off a ladder on his 
head, suffered a derangement of his pituitary secretion and 
grew ten inches that year and eight the next! These giants 
nearly all suffer from circulatory difficulties— the heart is 
strained trying to pump blood around so huge a frame. If 
the hyperactivity of the gland sets in after the growth zones 
of the bones are already ossified, then, instead of gigantism, 
growth is mainly confined to an enlargement of hands, feet, 
and face (acromegaly). Often this condition, in which the 
skin also tends to be too big for the body and to hang in 
great loose folds, and gigantism of some degree are associated. 
This is strikingly exemplified in certain breeds of dogs, such 
as the St. Bernard or the mastiff, with their huge jowls. This 
racial character of pituitary activity shows that if is genet- 
ically influenced to a considerable extent, both as to degree 
and time of onset. Human pedigrees indicate that the factors 
for tallness are multiple and mostly recessive. It is unlikely 
that all of them act through the pituitary. 

Conversely, underproduction of the pituitary growth hor- 
mone during development results in midget size, as in the 
familiar human hereditary type, or in bantam chickens. This 
is purely a dwarfing of skeletal size. There is a normal varia- 
tion of intelligence in these types. In animals, growth can be 
restored to normal if implants of active anterior pituitary 
tissue are made before the bones are "set," their growth zones 
ossified; but attempts to help human dwarfs by this means 
have not been entirely successful so far. The time of onset 
of the deficiency will clearly be very important here, just as 
in the case of hyperactivity. When the deficiency sets in after 
the trunk skeleton is completed, but while the limbs are 
lengthening, the result is deformity rather than a miniature; 
for the trunk and head are then of normal size, but the arms 
and legs are curtailed. This produces the "court jester" type 
of dwarf, the Pekingese dog, and similar types. This condi- 
tion is usually recessive in inheritance, while brachydactyly 


(short fingers), still later in onset and consequently much less 
deforming, is a dominant. These genetic types afford a good 
example of the way in which genes may produce their several 
effects by determining the relative times of the onset and 
duration of processes, just as in previous cases we have seen 
how they acted upon the relative rates of processes. 

It is evident that this hormone must be different from that 
of the thyroid, a deficiency of which during development 
also produces dwarfism, but with stunting of the intelligence. 
Thyroxin cannot replace a deficiency of the pituitary growth 
hormone. On the other hand, normal activity of the anterior 
pituitary is requisite for the development and normal func- 
tion of the thyroid, the parathyroids, the adrenal cortex, the 
ovaries oP testes, and other glands. It is the kingpin of the 
whole endocrine system. Its control over the thyroid is by a 
separate hormone; its regulation of the adrenal cortex prob- 
ably by still another. There is growing evidence that it regu- 
lates the insulin production of the pancreas, and the metabo- 
lism of fats. Whether or not its control over the parathyroids 
is by a hormone other than the growth hormone, is still 
rather uncertain. 

The three remaining hormones of the anterior pituitary 
are all associated with the development and functioning of 
the reproductive system, and can be better understood as we 
outline the development of this system. 


Our sex is determined, as we have already seen, at the very 
instant we are conceived. If the sperm contributing our pa- 
ternal heritage carries an X-chromosome, we become female; 
if it carries the smaller, gene-empty Y-chromosome, we be- 
come male. In spite of this genetic determination of our sex, 
however, we are more than six weeks on the road to birth 
before there is any further sign of sexual distinction. 



The gonads (ovaries or testes) 

It is not that development of the sex organs has not com- 


menced. They are well along, but so far completely alike i 
both sexes. Both ovaries (female) and testes (male) begin as 
projecting folds of the mesoderm just below the developing 
kidney ridges in the body cavity on each side of the intestine 


?mmi : 




" in 



Fig. 103. Origin of the gonad. A cross section of the kidney and genital 
ridges from a five- to six-weeks-old human embryo. (Redrawn with modifica- 
tions from Arey's Developmental Anatomy. Courtesy of W. B. Saunders 

(Fig. 103). The sex organs lengthen and round up. They sepa- 
rate from the kidneys, and, like the other organs, hang sus- 
pended from the dorsal side of the body cavity, in slings 
(mesenteries) of the membrane which lines it. 

Within the sex organs, at about two months after concep- 
tion, sexual differences appear. In males, cells within the 
testes become grouped into cords. These become hollow, 
making the testis tubules in which the sperms eventually 
arise. Each tubule has a sheath of connective tissue cells. 
Next to this are the prospective sex cells, which are not trans- 
formed into sperms until puberty. 


In females, no definite cords of cells form in the ovary, as 
they do in other animals or in males. Instead, the whole 
central mass of cells becomes recognizable as a group of 
prospective egg cells. Connective tissue invades these and 
breaks them up into small clusters. Most, or even all, of the 
prospective egg cells then degenerate, except those closest to 
the outside. Others arise from the germinal layer of cells 
covering the ovary. In the last few months before birth each 
egg becomes surrounded by a follicle, or capsule of nurse 
cells. As in the case of the sperms, the growth and meiosis 
of these prospective eggs are delayed until puberty. Shortly 
after birth the formation of additional egg cells stops. There 
is even, according to one investigator, a degeneration of great 
numbers. He estimated that at three years of age there are 
approximately 400,000, and that five years later this num- 
ber has been reduced to about 40,000, while at puberty there 
are even less. 

The sexual ducts 

The tubes or ducts through which sperms and eggs make 
their exit from the body are not growths from the ovaries or 
testes themselves. The male ducts, if not the female, are de- 
rived from the remains of the mid-kidney. 

The main mid-kidney ducts, one on each side of the body, 
open into that allantoic portion of the cloaca which becomes 
the urethra, below the urinary bladder (see Fig. 87). Par- 
allel, budding from a groove in the mesoderm covering each 
mid-kidney, a second pair of ducts develops, flaring into 
trumpet-like mouths at the head end. (In sharks these ducts 
arise by partitioning the main mid-kidney ducts, splitting 
them in two. This has led many embryologists to believe 
that this second pair of ducts traces back genetically to the 
mid-kidney ducts, and that its present origin in our bodies 
represents one of the developmental short cuts frequently to 
be found.) This second pair of ducts furnishes the rudiments 
for the female sexual ducts, while the original mid-kidney 



ducts become the sperm ducts. Whatever our sex, we thus 
start out in life equipped with both male and female sexual 

The external genitalia 

During the sixth week of our growth (Fig. 104^), a rounded 
hump appears just in front of the good-sized tail. On its sur- 








••• Urinary 

Scrotum*"- Membrane, 

* clos 1 ng Vagina 



Fig. 104. The embryonic development of the external genitalia. A, B, C; 
early, middle, and late stages in the indifferent period. D, male and female 
external genitalia after differentiation is well along. (Redrawn with modifica- 
tions from Parshley's The Science of Human Reproduction. Courtesy of 
W. W. Norton & Company) 

face, next to the tail, is a shallow groove, the floor of which is 
a thin membrane closing the urethra. (The anus just below 
this is also still closed by a membrane at this time.) 

A week later (Fig. 104.B), the hump has lengthened into a 


cylindrical phallus, with a rounded cap-like end known as the 
glans. At the base of the phallus are rounded swellings. The 
membrane closing off the urethra ruptures at about this time. 
(The tail has by now dwindled to a nubbin.) 

At eight weeks (Fig. 104C), the genitalia are just beginning 
to appear different in male and female. The urethral open- 
ing is now shorter, and in the male the portion which re- 
mains is farther out on the phallus than in the female. 
Meanwhile the phallus has grown considerably, and the glans 
is set off by a neck. 

Male and female 

What starts the differentiation of the ovaries and testes? 
This depends upon the chromosomal constitution, the prim- 
ary effect of which is not known, but may possibly be to fix 
the basal rate of metabolism at a higher level in males than 
in females, for this is an early and fundamental difference be- 
tween the sexes. 

We should remember that the gonads are basically so 
similar that an ovary may, under abnormal conditions, de- 
velop into a testis, producing one of those extremely rare un- 
fortunates, the human hermaphrodites, who have one ovary 
and one testis. Or, occasionally, disease may result in the 
destruction of a whole ovary or a part, whereupon it may be 
replaced by a testis. Well known is the instance of the Scot- 
tish hen who stopped laying eggs, metamorphosed into a 
rooster, and became the father of two chicks. Her one func- 
tional ovary-it is characteristic of female birds to have only 
one functional sex organ— had been destroyed by tuberculosis, 
and the other rudimentary sex organ had then developed into 
a testis. 

As the sex organs diverge developmentally they begin to 
function as endocrine glands, testes somewhat earlier than 
ovaries. The interstitial cells between the tubules of the testis 
produce the male sex hormone (testosterone), while the female 
sex hormone (theelin, or estrin), which accumulates in the fluid 



filling the follicles, has a source not specifically clear. These 
two hormones are very similar in chemical structure— they 
are both sterids— and the switch between them must be rather 
easy. In fact, both hormones appear to be produced in each 
sex even in adults, and the course of development, as was 
emphasized earlier (in Chapter IV), is determined by which- 
ever one predominates. The further development of the sex- 
ual ducts and genitalia (see Fig. 104) is influenced by which- 
ever sex hormone is present. 




Half a dozen or so of the mid- 
kidney tubules closest to each 
testis grow into it and make 
connections with the testis tu- 
bules. Lengthening considera- 
bly, these mid-kidney tubules 
and the upper portion of the 
main duct into which they open 
all lie coiled on the testis, form- 
ing the epididymis, a storage 
place for sperms. 

The female pair of ducts com- 
pletely degenerates, except for 
a tiny bit of the merged portion 
just at the bottom, and another, 
clinging to each testis, at the 

The mid-kidney tubules and 
ducts degenerate leaving only 

The funnel-shaped mouths of 
the female ducts (oviducts) fit 
over the ovary, ready to pick up 
any mature eggs released. The 
lower ends merge and thus give 
rise to the uterus and vagina. 
These, at first indistinguishably 
alike, become clothed with in- 
voluntary muscle, especially 
abundant about the upper por- 
tion, which becomes the uterus. 
The vagina, which at first opens 
into the urethra, is prolonged 
by a partition that grows down 
until vagina and urethra are 
completely walled off and open 


The phallus continues to 
lengthen until it becomes a 
penis. The opening on its un- 
derside is closed up and a new 
one appears at the tip. The 
two swellings on either side of 

The phallus remains short, 
consisting mainly of the glans 
portion, and is called the clito- 
ris. The swellings on either side 
remain undeveloped, as com- 
pared to the male, and make 


Male Female 

the base of the phallus enlarge the major lips, while the mar- 
into a sack, the scrotum, and gins of the urethral groove form 
the testes descend into this as- a pair of inner, minor lips. At 
sisted by the contraction of a the opening of the vagina there 
ligament fastening them to the is formed a perforated mem- 
bottom of the scrotum. brane, the hymeneal membrane. 

The quiescent period 

Sexual development is suspended from birth through 
childhood. Production of the hormones from testes or ovaries 
dies down. This is apparently due to the control exerted by 
the hormone from the adrenal cortex, which in its turn is 
controlled from the pituitary gland. It seems likely that the 
fairly frequent human "pseudohermaphrodites," who have 
ovaries but male external genitalia, result from an abnormal 
activity of the adrenal cortex before birth, as the hormone 
cortin is known to exert a strong impulse toward the devel- 
opment of male structures. At any rate, it is clear that ab- 
normal activity of the adrenal cortex during childhood may 
cause puberty to set in early. In boys this leads to remarkably 
early growth and maturity, both sexual and mental, so that 
even when one year old they may enter puberty, and by the 
age of five be ready to die as old men. Girls mature in a 
similar way, but with an added superimposition of male char- 
acteristics, such as a growth of beard and transformation of 
the external genitalia to the male type. 

This can hardly be the whole reason why sexual develop- 
ment is suspended in childhood. Other glands and their 
products may be involved; but we can hardly doubt that the 
adrenal hormone, cortin, helps to control the situation. 


At about fifteen years of age in boys, and a year or so earlier 
in girls— these ages are for our temperate clime; in warmer 
regions puberty sets in a couple of years earlier— the ovaries 



or testes resume production of the sex hormones. This brings 
to maturity the reproductive system, last of all the organ sys- 
tems to reach its functional level. Many parts of the body are 
affected. The larynx enlarges and the vocal cords lengthen, so 
that the voice becomes deeper, especially in males. Hair 
grows in the armpits and around the external genitalia, and 
boys commence to sprout a beard. 

The major changes in males are naturally internal, within 
the testes themselves. Here the prospective sperm cells begin 
to divide rapidly, then to grow, pass through the two meiotic 
divisions, and transform into sperms. As they go through 
these successive steps, they are pushed into the central cavity 
of each tubule by the newer cells being formed by mitosis 
beneath them. Once the sperms are mature, they pass, still 
passive, into their storage chamber, the long coiled epidid- 
ymis. The prostate gland, seminal vesicles, and other glands 
which lie around the sperm ducts, also become functional 
now, secreting a milky, odorous, alkaline fluid which vitalizes 
the sperms into activity when they come in contact with it. 
The mixture of fluid and sperms is known as semen. 

In girls the breasts enlarge, and the pelvis broadens so that 
its aperture is larger. These are vital preparations, as the 
fetus must pass through this bony ring at childbirth and must 
be nourished afterward. The broadening of the pelvis throws 
the hip joints out to the sides. Consequently the thighs slope 
in toward each other, and, to preserve the balance, the knees 
become angled instead of straight! (Similar but slighter al- 
terations occur in the shoulder, girdle and at the elbow.) 
These changes produce the typical female figure with its 
flowing curves, and result in the slight physical awkward- 
ness which handicaps most women in competing with male 

The internal changes are more important. The ovaries 
mature, and the early follicles, which have heretofore de- 
generated after reaching a certain stage, enlarge one by 
one. As each prospective egg finishes storing up its food sup- 


ply, it passes through the first division of meiosis, forming 
one minute "polar body." The follicle by now projects from 
the ovary as a sphere about the size of a small marble. It then 
opens, and the egg is released, along with its surrounding 
fluid, to be caught up by the mouth of the oviduct! Here 
it awaits fertilization, which must come within two or three 
days at most, as after that time degeneration will set in. 

Meanwhile changes have been going on in the uterus un- 
der the influence of the increased production of theelin by 
the ovary. The lining of the uterus becomes more glandular 
and more richly supplied with blood vessels day by day, and 
by rapid cell division becomes greatly increased in thickness. 
But the preparation for the reception of the fertilized egg is 
not yet complete. In the now empty follicle of the ovary there 
forms a clump of yellow cells (corpus luteum) that begin to 
produce a second ovarian hormone, progestin. Under the in- 
fluence of this hormone the glandular lining of the uterus 
commences to secrete a sticky fluid, which is necessary for the 
implantation of the fertilized egg in the uterus, and perhaps 
nourishes it before the blood connections are provided by the 
growth of the placenta. 

If the egg is not fertilized, the production of theelin by the 
ovary declines, the corpus luteum begins to degenerate, and 
then the whole superficial lining of the uterus sloughs off. 
This, accompanied by a loss of blood from the rupture of the 
rich supply of blood vessels in the lining, is menstruation, 
generally the first startling sign to a girl that she is approach- 
ing maturity. As the ripening of the follicles is limited to 
recurrences roughly once each lunar month (twenty-eight 
days), the menstrual cycle, with its frequent accompaniment 
of ill-ease during menstruation, sets in. 

Menstruation and ovulation (the release of the egg from 
the ripened follicle) are thus alternating phases of the cycle, 
the latter coming about nine or ten days after menstruation 
stops. (This varies individually from the twelfth to the 
twenty-first day after the onset of menstruation.) What regu- 



lates the cycle with such exactitude? What is responsible, in 
other words, for the rhythmic increase and decrease in the 
production of theelin by the ovary? At least a partial answer 
to these important questions has been found in the action of 
a hormone of the anterior pituitary. This also varies in a 
cyclic way, apparently because the theelin itself, as it in- 
creases in concentration, inhibits its production (Fig. 105). 

— Curve of production of pituitary hormone 

« » - - theelin. 

^ Time ofouula Hon 

f m I " " menstruation 

Fig. 105. Curves to show the relation of the production of the hormone from 
the anterior pituitary gland to that of the hormone from the ovarian follicles 
(theelin), and the consequent regulation of the cycle of menstruation and 
ovulation, as explained in the text. 

The growth of the corpus luteum is also stimulated by a 
hormone from the anterior pituitary, one which is produced 
during the intervals when the theelin-stimulating hormone 
is inhibited. 


The impulse to seek a mate, the sex urge, comes from the 
presence of either male or female sex hormones in the blood. 
Females among the lower mammals, however, are receptive 
only at the height of theelin secretion. They come period- 
ically into "heat," as for example, twice a year in dogs, every 
three weeks in cows, every week in mice. As this is the period 
of ovulation, here evidently is nature's method of insuring 
pregnancy. But note the effect on the male! He is usually 
interested in a female only while she is in "heat"; as soon as 


she has passed the period, he is off to another. The "family," 
in our sense, does not exist among the lower mammals. Either 
the female rears her cubs alone, or some powerful bull gathers 
a whole harem of females about him, keeping them his by 
furiously fighting off all younger upstarts. In our species, 
however, this physiological limitation of receptiveness on the 
part of females to certain periods has disappeared, and the 
human monogamous family became possible. 

The act of mating (coitus) is itself one of nature's great 
economies, insuring the highest percentage of fertilization 
and pregnancy. The pleasurable erotic sensations, widely dif- 
fused over the body, but centered in the stimulation of the 
glans of penis or clitoris, contribute toward insuring repro- 
duction. In the act of mating, a vast quantity of sperms- 
several hundreds of millions— are expelled from the epididy- 
mis, and mixed with the secretions from the prostate and 
other glands, which render them active. The semen is then 
deposited by the erected penis in the female vagina. (Both 
penis and clitoris contain spongy bodies which stiffen by 
means of an influx of blood under sexual excitement.) The 
sperms then swim by their own efforts up through the uterus 
and along the female sexual ducts until they encounter the 
egg. This direct transmission of sperms from the male to 
the female is a far more effective way of insuring fertilization 
than the method employed by fishes and frogs, whose eggs 
are first laid in the water and then have the sperms poured 
out near them. In land animals, consequently, fewer eggs 
need be produced, since there is little waste from lack of 
fertilization; and, as the egg carries considerable stores of 
food, this is an important saving. 

A second and perhaps more important relation is that 
fertilization of the egg before it passes down the oviduct 
enables it to be covered with additional layers of food and 
with a protective shell before it is laid. This would appear 
to be of little importance in mammals, but mammals have 


evolved from reptiles, to whom this ability must have been 
of primary importance in their conquest of the land. 


The, story of the descent of the fertilized egg to the uterus, 
and of its implantation and development there, has already 
been told. Here we are concerned with the mother's part. 
The most important warning of pregnancy is the omission 
of menstruation. Why does upset of the regular cycle occur? 

Somehow the implanted embryo stimulates the corpus 
luteum to keep on growing, and this, if we can reason from 
what is true in rabbits, dogs, and guinea pigs, is necessary to 
prevent an abortion. Under the influence of the progestin, 
the lining of the uterus, instead of sloughing off, continues 
to thicken and prepares to take part in the formation of the 
placenta. After about three weeks, though the corpus luteum 
continues to grow, it is no longer essential; from the time 
when the placenta is developed, menstruation is apparently 
checked by the production of theelin there. 

Slowly the production of theelin rises, until late in preg- 
nancy there is considerably more of it in the blood than at 
times of ovulation in the regular cycle. The anterior pituitary 
hormone is thought to be responsible for this. It increases 
in amount up to the fifth month, and then declines. The 
cycle rather resembles a regular menstrual cycle stretched 
out to ten times its usual length (Fig. 106). 

These two hormones are so abundant in pregnant women 
that considerable quantities are present in their urine. In 
fact, such urine furnishes an important source of supply of 
theelin for medical and experimental use. Moreover, by in- 
jecting the urine into female rabbits or other test animals, 
an accurate test for pregnancy has been found even in the 
first month. 

The anterior pituitary steps up its production of the 
growth hormone, and the thyroid and adrenal cortex, too, 



become more active. These conditions seem to be for the 
benefit of the embryo. The strain on all the endocrine glands 
at this time is severe, and may lead to upsets and disturbances. 
Supplies of iodine, calcium, insulin, and the vitamins must 
be kept adequate. "Pregnancy," says Hoskins, "is a condition 
exquisitely dependent upon endocrine factors." 

The mounting tide of theelin sets up a renewed develop- 
ment of the breasts. Then, toward the end of pregnancy, the 
anterior pituitary commences to supply another hormone, 

Curve of production of 
.pituitary hormone 
.Curve ofproduction of theelin 



Fig. 106. Curves to show the relation of the production of anterior pituitary 
hormone to the production of theelin during pregnancy. 

prolactin, which stimulates the mammary glands to prepare 
for the active secretion of milk. So potent is it that it will 
evoke milk production even in male rabbits and guinea pigs 
if their breasts are first stimulated to develop by injections 
of theelin and progestin. 

At last, labor and childbirth! Then once again is resumed 
the cycle of ovulation and menstruation. One further point 
we should like to know. Why is it that only one egg is 
normally permitted to mature at a time, while in some lower 
animals litters of more than a dozen are produced? Obvi- 
ously, the human uterus is not really adequate to accommo- 
date a large number of embryos, as is that of mammals like 
mice or rabbits, in which the embryos develop in the "horns" 
of the uterus (that is, in the lower portions of oviducts). It 


is clear, too, that the tendency to have twins or other multiple 
birt hs runs in families. Primates — monkeys, apes, and man- 
like some other groups, must have acquired genes that, in 
line with the extended term of pregnancy, limit the number 
of eggs maturing at one time, and so cut down multiple 
births. But how these genes act— through what endocrine 
hookup or otherwise— we have not yet discovered. 

We have now completed the great cycle of a human genera- 
tion, from conception to contributing to conception, from 
birth to giving birth. This is the story of the continuity of 
life through genes and protoplasm, and of its unfolding as 
genes interact with their environment. Now seeming direct 
and foresighted, now circuitous and wasteful, this early de- 
velopment of ours is the basis of our later capabilities and 
handicaps, similarities and differences, needs and problems. 
By learning its conditions, we may be enabled to lay the best 
possible foundations. 

Yet our responsibility is broader than the immediate one of 
reproducing our kind. The longer our young remain imma- 
ture and dependent, the longer will we adults be concerned 
with their care, and our biological responsibility be protracted. 
Here social and economic factors necessarily begin to concern 
us. In the world of today life is becoming so complex and so 
dangerous that ever greater parental care is called for, ever 
longer training is required to make our children self-suffi- 
cient. The generations are stretching out. Man as an animal 
might mate on the average at sixteen or eighteen years of age; 
as a social creature he is mating at twenty-five— perhaps, in a 
few more years, at thirty. The biological changes in the 
middle-aged and the old are becoming more and more im- 
portant. What do we know about them? To this subject our 
final chapter will be devoted. 


On Growing Old 

CHILDREN born in 1850 could expect to live, on the 
average, to the age of forty. Today's babies have a life 
expectancy of sixty years, and tomorrow's may hope to attain 
an average of seventy to seventy-five. The noted authority 
on American vital statistics, Dr. Louis I. Dublin, has shown 
that this gain in life expectancy applies almost entirely to 
those under the age of forty. For example, males born in 
1901 had a life expectancy of forty-eight years; those born in 
1930, of fifty-nine years— a sizable increase. Yet, while in 1901 
men forty years old might have expected, on the average, 
2734 additional years of life, in 1930 men of forty could ex- 
pect only 28i/£ additional years of life. For women virtually 
the same is true, although the gain in life expectancy con- 
tinues for a few more years. The conclusion is inescapable. 
"The greater part of the gains in the expectation of life at 
birth may be attributed to the control of infant mortality, to 
the practical elimination of certain diseases of childhood, and 
to the curtailment of conditions once considered typical of 
adolescence and early maturity. Altogether our progress with 
the diseases of late maturity and old age has not been of any 
consequence. To date we have not been able to stretch the 
life span." 1 

In considering questions of ageing and death, we must ac- 

1 Dublin, Louis I. Problems of Ageing, p. 107. E. V. Cowdry, Ed. Williams 
& Wilkins, Baltimore, 1939. 




cordingly deal with two distinct sets of problems, the one 
concerned with health and disease, the other with natural 
senescence, that is, with the wearing out of physiological 


We owe the great increase in the life expectancy of those 
under forty that has been made during the last century pri- 
marily to Louis Pasteur, for his discovery that many diseases 
are due to bacteria opened the way for successful campaigns 
against those diseases. "Since 1880 .. . typhoid fever and diar- 
rhea and enteritis have diminished almost to the vanishing 
point in many communities; cholera and typhus fever are 
rarely causes of death in this country to-day; the incidence 
and deaths from diphtheria have been greatly reduced; small- 
pox is under control in all communities where vaccination is 
practised; bubonic plague, though endemic in certain re- 
stricted areas, is not responsible for many cases of disease or 
many deaths; the infant death rate has been diminished more 
than 75 per cent.; the death rate from tuberculosis, at one 
time the most important single cause of death, has been re- 
duced 75 to 80 per cent.; hookworm is controlled in the 
South; yellow fever is now non-existent in this country; and 
malaria is under better control." 2 Approximately 768,000 
lives are saved annually among the white population of the 
United States as a result of the curtailment of the death rate 
since 1900. 

To a great extent the initial achievements in this battle with 
disease have resulted from the discovery of specific germs and 
their avenues of infection. Our knowledge of the importance 
of mosquitoes in transmitting malaria and yellow fever, of 

2 Horwood, M. P. "An Evaluation of the Factors Responsible for Public 
Health Progress in the United States." Science, Vol. 89, pp. 517-526, June 9, 



flies in spreading the germs of typhoid fever, cholera, dysen- 
tery, and other intestinal diseases, and of rats, fleas, and lice 
in conveying the agents of plague and typhus made rapid ad- 
vances in the control of these maladies possible. General sani- 
tary measures were taken to prevent the pollution of water 
and milk supplies, and the screening of houses and warfare 
on vermin have made the notorious epidemics of past centuries 
a half-forgotten nightmare. Equally valuable in controlling 
the inroads of larger parasites have been such discoveries as 
those that hookworms enter through bare feet and that 
trichina worms and tapeworms enter by way of half-cooked 
infected meat. 

In another direction progress has also been marked— in the 
search for ways and means of destroying germs. Outside the 
body, this was simple. Heat proved a perfect sterilizing agent, 
making it easy to inaugurate the new day of aseptic surgery. 
The skin, too, is able to withstand many harsh and effective 
antiseptics, such as alcohol, carbolic acid, and iodine. On the 
other hand, it turned out to be considerably more difficult to at- 
tack germs once they have gained access to the body, without 
at the same time harming blood and tissue cells. Here the 
agent must be chemical, yet nontoxic for us in doses that are 
toxic for our invaders. Quinine for malaria and Ehrlich's sal- 
varsan for syphilis remained for years the only notable specif- 
ics of this character. The recent discoveries of the great value 
of sulfanilamide, sulfapyridine, sulfathiazole, sulfaguanidine, 
and sulfadiazine in combating invasions of cocci have given 
new life to this effort. To be sure, the use of these drugs is 
not without certain dangers. Nevertheless, the death rate 
from pneumonia has already been reduced 90 per cent. 
Blood poisoning, streptococcic sore throat, gonorrhea, menin- 
gitis, wound infection, and peritonitis from a ruptured appen- 
dix or after abdominal surgery, together with a long list of 
other infections, are now readily conquered. In addition to 
these almost magical drugs, new substances are being discov- 
ered, some of which offer even more promise than the sulfa 


drugs. There are allantoin, obtained from fly maggots, 
gramicidin that comes from bacteria in the soil, penicillin, 
extracted from a common green mold, and several others 
that may in time become as familiar to us as sulfanilamide is 
already. These discoveries open a new chapter in the story 
of man's struggle with the germs of disease. 

Diseases spread by the mouth spray of human carriers have 
also been successfully attacked. Here Pasteur's immunization 
methods, worked out originally for the bacterial disease an- 
thrax and for virus-produced rabies, have proved to be of 
most value. Diphtheria, meningitis, infantile paralysis, scarlet 
fever, measles, and certain types of pneumonia have been 
conquered through the use of immune serums. A promising 
new serum for typhus, that scourge of wartime, awaits whole- 
sale testing. 3 

Another class of diseases has been traced to nutritional de- 
ficiencies, and these have proved in the end easiest of all to 
conquer. Beriberi, scurvy, and pellagra are on their way to 
join smallpox and "The Black Death" among former scourges 
of mankind no longer to be feared. 

There remains a group of diseases we have been but poorly 
successful in combating. Some of these are respiratory dis- 
eases—influenza, tuberculosis, 4 the common cold. For these 
no satisfactory serums have been produced, and as yet no 
chemical specifics have been found. Others of the group we 
may term functional diseases, since we know very little of 
their primary causes, other than that they are noninfectious. 
The most important of these are cancer, diseases of the heart 
and blood vessels, kidney disorders, the allergies, and insanity. 
Of all such diseases only diabetes has really been overcome. 

3 For more extensive consideration of these subjects, see F. L. Fitzpatrick, 
The Control of Organisms, Chaps. II-VI (Bureau of Publications, Teachers 
College, Columbia University, New York, 1940). 

4 Although the death rate from tuberculosis has been reduced 75 to 80 
per cent, as quoted above, this disease still ranks seventh among the causes 
of death in our country. 


Cancers and cardiovascular 5 and kidney diseases account for 
nearly one half of all deaths. Colds, allergies, and insanity, 
although as a rule not fatal, produce temporary or permanent 
incapacity that in the aggregate means an enormous economic 

The great difficulty experienced here is variability. Each of 
these is not a single disease, but a multitude of diseases, of com- 
plex and varied origin. There are at least thirty-two different 
types of pneumonia; there are many varieties of cancer; there 
are innumerable allergies; and so on. This is not solely be- 
cause of the multiplicity of causal agents. By far the greater 
difficulty arises from constitutional differences. Fortunately 
for the progress of medicine, we have heretofore been able 
to ignore such factors in dealing with most diseases— that is. 
the latter fall into the category of differences due to environ 
ment that are manifested in practically all genotypes (cate- 
gory 4, Chapter IV, p. 212). But now, the time has come 
when we must devote increasing attention to the category of 
environmentally caused differences that are manifested only 
in a restricted range of genotypes (category 3). To do this, 
medical science not only must shift its experimental attack, it 
must also combat the rather widespread failure of medical 
men to recognize that the question of constitutional differ- 
ences has great importance. A medical school that provides 
any acquaintance with human genetics is still a rare excep- 
tion, and only recently has the study of heredity even been 
recommended as a desirable addition to premedical training. 

Students of immunity and allergy, and researchers working 
upon the nature of cancer have been among the first to realize 
the necessity of dealing with constitutional differences. The 
importance of these has been impressed upon them by a num- 
ber of observations such as the following. Gray mice prove 
more resistant to streptococcus or pneumococcus infection 

5 The cardiovascular diseases include the chronic heart diseases, angina 
pectoris, arterial diseases, cerebral hemorrhage, and paralysis unspecified as 
to cause. 


than white mice. Black rats are far more resistant to anthrax 
than white rats. Susceptibility to specific types of cancer is 
definitely hereditary in experimental animals. The produc- 
tion of antibodies in similarly inoculated animals may differ 
enormously. Eskimos and Negroes show a high susceptibility 
to tuberculosis when living in a temperate climate under 
civilized conditions. Whites are more susceptible to yellow 
fever than blacks. Many diseases, long endemic in certain re- 
gions and among particular peoples, become epidemic and 
far more fatal when introduced elsewhere. This appears to 
be true of measles, smallpox, and syphilis, in addition to the 
other diseases we have just mentioned. When identical twin s 
have cancer, both have the same type in the same organ at 
the same age. In general, the same type of tumor affects the 
various members of a family. 

Such evidences of the hereditary basis of susceptibility to 
disease have been further strengthened by occasional demon- 
strations of the exact character of the genetic mechanism. Sus- 
ceptibility to diphtheria has been shown to depend on a sim- 
ple recessive gene, and the same appears to be true of scarlet 
fever. The inheritance of resistance and susceptibility to 
tuberculosis depend on one or two genes only. Common dia- 
betes is due to a simple recessive factor. All allergies, includ- 
ing hay fever, asthma, eczema, hives, and food idiosyncrasies, 
appear to depend on a single, nonspecific, dominant gene, 
responsible for the heightened capacity to become sensitized, 
while the form in which the allergy is manifested is de- 
termined partly by exposure and partly by modifying genes. 
But the irregular type of manifestation that results from 
hereditary susceptibility plus environmental exposure to a 
stimulus has been exceedingly difficult to analyze. 

These immunities, susceptibilities, and allergies reside 
partly in the ability, or lack of ability, of the blood or tissues 
to produce specific antibodies that are carried in the blood; 
and partly in changes of the cells themselves, changes of which 
we know little, but which may be thought of as due to the 


formation of antibodies that are not liberated. 6 The ca- 
pacity to produce antibodies, whether free or unliberated, 
may be exercised as a normal feature of development; on the 
other hand, it may remain unexercised until after exposure 
to the proteins that act as antigens. The antibodies of the 
blood groups belong in the first category. Susceptibilities and 
immunities to some diseases are also innate, but in many 
cases— measles and mumps, for instance— immunity develops 
only after an attack of the disease. Allergies, cancer, and in- 
sanity appear to belong nearly always to the second category. 
The distinction between these categories is of very great im- 
portance. We can do very little to control the conditions of 
prenatal development, and consequently in the relative con- 
stancy of the prenatal environment the genotype is rendered 
the decisive factor. Thus, as we have seen (p. 95), the blood 
groups, in the common sense, are inherited. Those traits 
which mature in the highly variable postnatal environment 
tend to be decisively affected by it. The final factor in the 
development of a specific immunity or allergy is commonly 
exposure to the specific antigen; the final factor in the de- 
velopment of a cancer is commonly chronic irritation; the 
final factor in the development of manic-depressive insanity 
is commonly a great emotional strain. 

Here then, where we are dealing with acquired immuni- 
ties, allergies, and functional disorders, since the final factor, 
the environmental one, is decisive, they are nonhereditary 
in the common sense. Early in the history of immunology, 
Paul Ehrlich demonstrated this. He showed that, in mice, 
an acquired immunity to protein poisons could be trans- 

6 It has been known for a long time that only proteins can act as antigens, 
that is, as substances which stimulate the production of antibodies. Workers 
at the Rockefeller Institute in New York have recently demonstrated that 
the specific character of the antigen-antibody reaction is due to the presence 
of complex sugars (polysaccharides) attached to the protein molecule. Alone, 
the sugars have no immunizing effect. Attached to protein molecules, each 
specific sugar stimulates the production of its specific antibody, regardless 
of whatever differences may exist in the much greater protein part of the 



mitted maternally but not through the sperm, and that im- 
munity transmitted in this way is evanescent, and cannot be 
passed on to a second generation. Already in the offspring it 
is but a passive immunity, a mere transmission of the free 
antibodies themselves from mother to offspring, either after 
birth by way of the mother's colostrum 7 or milk, or before 
birth through the placenta, or perhaps even— though this is 
doubtful— by way of the egg cytoplasm. In any case, the 
transfer of free antibodies is to be sharply distinguished from 
the transmission of genes which lead to the development in 
the young of their own capacity to form antibodies. The 
former essentially resembles numerous artificial measures of 
therapy, such as the hypodermic injection of a dose of the 
diphtheria antitoxin produced by immunizing horses. 

Active immunity, on the other hand, rests upon a genetic 
basis, whether it is innate or acquired, that is, whether it is a 
natural feature of development or whether it remains as an 
undeveloped potentiality until after exposure to certain ex- 
ternal factors. Here we can see very clearly how hereditary 
and environmental factors are inherently involved in pro- 
ducing a trait. 

Death from violent accident has in recent years become a 
very important item in our mortality figures. It now ranks 
in fifth place as a cause of death, just below influenza and 
pneumonia (together) and the kidney diseases. Automobile 
accidents alone kill nearly twice as many people today as does 
appendicitis. At first we might think that in accidents the 
environmental factors would always prove decisive. Yet few 
accidents are wholly external in causation. The constitu- 
tional factor is generally of great importance, some people 
being far more prone to suffer accident than others, and of 
those who meet equal mishaps some being far more severely 
injured than others. Heredity, past development, experience, 
external circumstances, and chance are all inextricably con- 

7 Colostrum is a watery fluid which precedes by a day or two the secretion 
of real milk. 


cerned in determining the outcome. Let us consider a perti- 
nent example. Each person has characteristic speeds of re- 
action. Thus the braking reaction important in driving a car 
takes, on the average, about half a second, measured from a 
signal given the driver when his foot is on the accelerator to 
his application of pressure on the brake pedal. The reaction 
time does not vary with the speed of the car, hence at 60 
miles per hour an average driver, perceiving danger, will 
cover forty-four feet before he can even begin to check his 
speed. The reaction time of an individual does vary with 
practice, with age, and with fatigue, but the minimum re- 
action time is characteristic for each individual. It is inher- 
ent, a function of his development, the product of his genes 
and their environment. Who would doubt that this has a 
great deal to do with the incidence of automobile accidents? 
One's fitness to drive a car, then, or more broadly, one's abil- 
ity to avoid accident in any kind of dangerous situation— 
these depend on innate factors that we ignore only to our 

Should these facts make us fatalistic? That there are heredi- 
tary factors of importance among the causes of disease or ac- 
cident does not mean that we can do nothing to cure or 
avoid them. On the contrary, to know that an individual's 
reaction time is important in determining whether or not he 
is a safe driver should surely enable us to formulate better 
measures for preventing automobile accidents. People with 
abnormally slow reaction times ought to be kept out of haz- 
ardous occupations. Common diabetes is hereditary, but doses 
of insulin readily alleviate it. Susceptibility to diphtheria is 
hereditary, but diphtheria antitoxin is, nonetheless, a potent 
curative. Why should the knowledge that the tendency to 
develop cancer may also be hereditary strike terror to our 
hearts? Actually, the fact that a chemical chain-reaction must 
lead from the genes to their end-product offers additional 
points at which the problem may be attacked and brought 
under control. Let us merely be clear in our minds that, hav- 


ing cured an individual's cancer, schizophrenia, or epilepsy, 
we have not altered any genes that might be concerned, and 
that these may yet be passed on to a new generation to wreak 
havoc upon occasion. 

Finally, what are the possibilities of further extending our 
life expectancy in the future? How long, on the average, may 
we hope to live if there is an appreciable improvement in our 
control over the cardiovascular and renal diseases, over can- 
cer, tuberculosis, influenza, and pneumonia? About 7.35 years 
might be gained from the complete elimination of the first 
two— but, of course, complete elimination is merely hypo- 
thetical. The elimination of cancer would add 1.45 years, of 
tuberculosis 1.1 years, of influenza and pneumonia about 1.4 
years. Complete elimination of death from accident would 
add 1.5 years to the average life span. 8 While such an achieve- 
ment must remain theoretical, an average life span of seventy 
years appears to be attainable in the near future. What this 
means in terms of the number of survivors and of the increased 
expectancy at each age is shown in Fig. 107, which also shows 
the gains made in the United States along these lines in the 
period between 1901 and 1930. 



We are just beginning to distinguish between ageing and 
disease, to appreciate that distinction between them made 
in the last section.. The ultimate, the decisive, factor in dis- 
ease is from without, the action of pathogenic organisms, 
malnutrition, or excessive strain. On the other hand, suscep- 
tibility to particular diseases or disorders is a matter of con- 
stitutional differences, varying from person to person and al- 
tering with age. Thus far, in striving to lengthen the human 
life span, we have merely learned how to avoid some of the 

8 Most causes of death affect the two sexes about equally, but males are 
far more prone to fall victim to accident than females. On the other hand, 
women are considerably more subject to cancer than men. 


NUMBER living MALES & FEMALES COMBINED number , living 
100,000 K4444- L. 







10 20 30 40 50 60 70 60 90 100 



Fig. 107. Comparison of survivors and of expectations of life at specified ages 
for the United States in 1901, 1930, and in the hypothetical future. (From 
Dublin and Lotka's Length of Life. Courtesy of Ronald Press Co.) 

external factors that accelerate ageing. We have made no 
progress in learning how to slow down the inherent ageing 
process itself. What has really been discovered about the lat- 

It is evident, to start with, that each animal species has its 
own characteristic life span. A rat is ancient at three years, 
a horse at thirty, a man at one hundred, a Galapagos tortoise 


not until about five hundred. We are more immediately in- 
terested in the variability within a species, to be sure, and 
would like to know to what extent that is fixed and how far 
it is modifiable. Yet, if we can gain some inkling why one 
species lives on the average two years and another two hun- 
dred, that would very likely throw considerable light also on 
the nature of intraspecific variability in the life span. 

The life span must obviously be correlated with the other 
physiological processes that are characteristic for each species. 
It cannot stand apart. It but marks the duration of that un- 
broken sequence of physiological and structural changes tak- 
ing place in every organism, of which early growth and de- 
velopment comprise but a segment. "We must all be born 
again atom by atom from hour to hour, or perish all at once 
beyond repair," said Holmes. Numerous recent studies with 
nutrients made artificially radioactive bear out his words. 
Even the bones and teeth, most permanent of all the parts 
of our bodies, are in constant flux. Could ageing fail to be 
determined by the nature of the earlier processes? The more 
rapidly growth and differentiation occur, the sooner must 
maturity be attained, and the earlier will senescence encroach 
upon it. The slower one lives and changes, the slower one 
grows— and the longer one may hope to live. A dormant seed, 
a bacterial spore, an encysted animal— these may live for cen- 
turies, it would seem. Small organisms vitrified by extreme 
cold and refrigerated appear to be potentially immortal. Or 
life may be prolonged by reversing the direction of growth. 
It is a fairly common experiment in biological laboratories to 
make planarian flatworms "grow younger" simply by starv- 
ing them, for this brings about a decrease in their size and 
dedifferentiation of their tissues, processes which feeding will 
again reverse at any time. Cantaloupe seedlings that are 
germinated on agar, without any nutrients whatever, at first 
grow vigorously, then remain in suspended animation for a 
while, and thereafter gradually die. There is a high degree of 
negative correlation between their rates of growth during the 


growing period and the total duration of their lives (—.5 or 
—.6). The faster they grow, the sooner they die. Also, the 
faster they grow, the higher their expenditure of energy, their 
rate of metabolism. With rats it is the same. When retarded 
in growth by being kept on a maintenance diet, they still ap- 
pear young at an age of 700 or even 1,000 days, while those 
that grow up normally are already aged or dead. When re- 
turned to a diet adequate for growth, the stunted rats will 
grow at a normal rate and mature in nearly normal fashion, 
except that they seem unable to attain quite the usual size. 
Evidently organisms grow old fastest while they are living 
most intensely and developing most rapidly. 

The relation between the basal rate of metabolism and the 
life span is also to be found in comparing the two sexes. The 
difference between the metabolic rates of males and females is 
negatively correlated with their duration of life. This is true 
for water fleas (Daphnia); it is true for man; presumably it is 
a general phenomenon. 

One school of biologists holds that these facts are indicative 
of an inherent ageing process in the life-substance itself. 
Protoplasm is a very unstable union of proteins and lipoids, 
they say, an elaborate colloidal system easily destroyed by 
whatever chemical and physical agents act on proteins or 
lipoids. Such colloids appear to lose their power to adsorb as 
they grow older. Their capacity to take up water also di- 
minishes and they shrink irreversibly. Gradually they lose their 
stability and become less reactive— and this is the basis of 
senescence. Destroy the dispersion medium of the colloidal 
system, disrupt the unstable protein-lipoid compounds, coag- 
ulate or dissolve out essential materials— metabolism will be 
paralyzed, and death supervene. 

This conception serves to explain why we shrink in weight 
and decline in stature as we become elderly— our colloids are 
losing their capacity to bind water. It also makes clear why 
younger individuals metabolize at a higher rate per unit of 
body weight, since their colloids possess maximum reactivity. 


It explains why poikilothermic 9 animals have a life span 
which varies inversely with temperature, for it can be shown 
that colloids age more rapidly as temperature goes up. Maybe 
the often fatal hardening of our arteries is due to the loss of 
resiliency and flexibility on the part of the colloids that make 
up the elastic tissue of the walls of the blood vessels. Perhaps 
this is why the old adapt themselves less quickly and effec- 
tively than do younger people to virtually all changes, both 
internal and external, with "a curious kind of faltering or in- 
decision in regulation. . . . The homeostatic mechanisms be- 
come more and more restricted in their ability to maintain 
the essential stability of the blood." 10 

Other biologists feel that this concept of ageing and death 
is probably too simple. Certainly our investigations have not 
gone far enough to prove the causal relation of changes in 
the body colloids to any of the characteristics of ageing. The 
theory also appears to ignore the potential immortality of 
relatively undifferentiated cells. Among unicellular animals, 
some strains are able to continue living and reproducing in- 
definitely, even without recourse to that process of endomixis 
whereby other strains replace their macronucleus by a fresh 
one from a reserve store, the micronucleus. In the former, 
favored genotypes, the hourly repair of the protoplasm and 
the elimination of wastes are apparently in balance with the 
destructive forces, and no drastic regeneration or rejuvenes- 
cence is necessary. To be sure, strains of other genetic consti- 
tutions are less well balanced. Some of these tend to degen- 
erate, and will die out except for the renovation of endomixis. 
For others not even this suffices— from their origin they 
are doomed to inevitable extinction, even in the most 
favorable of environments. Do not facts such as these mean 
that ageing and death result from the failure of repair and 
elimination to keep pace with exhaustion, dissolution, and 

9 Poikilothermic organisms are those without the capacity to regulate their 
body temperature. Their rate of metabolism consequently varies with the 
temperature of their external surroundings. 

10 Cowdry, E. V. "We Grow Old." Scientific Monthly, Vol. 50, p. 53, 1940. 


the accumulation of wastes? Many think so, and point to the 
experimental work of Alexis Carrel, Lecomte du Noiiy, and 
others as additional proof. 

Carrel was the first to develop successful methods for con- 
tinuously culturing the tissues of higher animals in vitro. He 
did this by growing the cells in a mixture of embryonic juice 
and blood plasma that was carefully controlled to prevent 
bacterial infection and to maintain favorable conditions, and 
by then transferring a portion of the tissue to fresh fluid every 
two or three days. Growth of the tissues by cell division is 
kept up at a stupendous rate. They double about every two 
days, as long as their nutritive medium is kept fresh. If, how- 
ever, they are not transferred, death will occur in a very few 
days, as the cells in the interior of the growing mass are in- 
creasingly cut off from food and air, and their wastes are ex- 
creted but slowly through the surrounding cells. Toxic 
substances accumulate and upon the death of cells in the in- 
terior are released, poisoning the others. Carrel was led from 
these observations to study what effect the age of the animals 
from which the plasma was taken would have upon the 
growth of cells in tissue-cultures. He found that the older 
the animal from which the supply came, the shorter the time 
cultured cells would survive in it. Evidently, with age blood 
undergoes some form of chemical change that tends to in- 
hibit growth and cell division, and to put a term to life. For 
a variety of birds and mammals, including man, there is a 
logarithmic inverse proportionality between increasing dura- 
tion of life and declining rate of growth (Fig. 108 A). 

This helped to explain one of Carrel's earlier experiments. 
A decrepit dog, nearly eighteen years old, had been anes- 
thetized and bled. Nearly two thirds of his blood was 
removed, the red cells were centrifuged out, washed, recentri- 
fuged, mixed with fresh Ringer's solution to restore the orig- 
inal volume, and then reinjected into the dog. After he began 
to recover from the shock of the operation, the procedure was 
repeated a second time. The almost complete replacement 


3 6 3 

-150 1 









> 6 \MELK3 









— \ 







1 234 5678 3 





Dotted Curve 
is extrapolated 























10 20 30 40 50 


Fig. 108. A, the relation between the age of animals from which serum was 
taken and the rate of growth of cells (fibroblasts) cultured in that serum. 
B, the relation between the age of a patient and the rate of healing of his 
wounds (cicatrization). (Redrawn from du Nouy's Biological Time. Courtesy 
of The Macmillan Company) 

of the blood plasma of the aged dog by fresh Ringer's solu- 
tion had the most startling results. The dog's appetite im- 
proved, "he ran and barked, a thing he had not done for 
years. His eyes were clear, his eyelids normal. His coat started 
to come in; he was gay, active, and most important of all, he 
was no longer indifferent to the charms of the other sex." n 
He was rejuvenated. 

Lecomte du Nouy, of the Pasteur Institute, made studies 
during the World War of 1914-18 that indicate a parallel 
decrease with age in the rapidity with which wounds of a 
given area heal over (Fig. 108JB). It is possible to predict 
with great accuracy, for a man of any given age, how long it 

n Lecomte du Noiiy, P. Biological Time, p. 115. Macmillan, New York, 
1937. This book also reports the experimental work mentioned here. 


will take a clean, noninfected wound of a certain area to heal. 

Studies like these have led a number of biologists to the 
concept of physiological time— time measured not by the revo- 
lutions of the earth around the sun or its rotation on its axis, 
but by the very changes within each organism itself. Since 
these changes do not proceed uniformly, since the rate of 
growing and living declines as age increases, a sidereal year 
represents very different relative values in this biological time 
at different absolute ages. It appears that the value of a year 
at any age is about equal to its proportion of the total life up 
to that age, so that a year to a child of ten has approximately 
four times the value of a year to a person of forty, and six 
times the value of a year to a person of sixty. To put it an- 
other way, time seems to flow more slowly to the young. Each 
of us can readily recollect the seemingly interminable way a 
year stretched from one Christmas to the next when we were 
seven. Endless hours filled each of those childhood days; 
swiftly they speed past us now. These experiments show that 
our memory has not played us false. Our sense of time is not 
based on clocks or stars or even the alternation of day and 
night, but on the changes within us as we grow and develop. 

But growth and differentiation do not proceed uniformly 
for the body as a whole, as we have seen, and neither does 
ageing. The thymus gland begins to decline at puberty. So 
do the tonsils and other lymphoid tissues, the tonsils usually 
becoming senile by the time we are fifty or sixty years of age. 
The reproductive organs cease activity at menopause in wom- 
en; and the prostate gland of males, an important factor in 
their sexual activity, is old at sixty. Bones and cartilage suffer 
from a progressive loss of mineral content, and become more 
brittle. There is on the whole less tooth decay, but the gums 
recede and teeth are more fully exposed and tend to be lost. 
Muscles acquire a proportionally greater amount of connec- 
tive tissue. The skin atrophies, and folds and wrinkles appear 
as its elastic tissue degenerates and the subcutaneous fat de- 


posits are withdrawn. The hair grays and falls out. The nails, 
especially the toenails, tend to thicken and become deformed 
as their rate of growth slows down. Hearing for tones above 
high C becomes impaired. Even within a single organ there 
may be differences in the ageing process. In the brain, for 
instance, white matter suffers more than the gray, and the 
frontal regions more than the more primitive parts of the 

These are nonvital functions. The heart and blood vessels 
are usually first of the vital systems to succumb— there is thus 
a reasonably sound basis for the saying that "a man is as old 
as his arteries." On the other hand, some systems show little 
or no sign of decline. It has been said on good authority that 
"the possible length of useful life of the visual apparatus is 
at least 120 to 130 years," 12 that the digestive system too is 
good for more than three score years and ten. 

We should not overlook the fact that the rates of ageing of 
many organs and systems are interdependent. The endocrine 
glands exert a potent influence over other systems in this re- 
spect. Perhaps the brain and nervous system would function 
indefinitely were it not for the failure of their blood vessels. 
Whether the kidneys might last longer than they do, if their 
elaborate circulation only held good, cannot be said. Perhaps 
the nurture of isolated organs in the Carrel and Lindbergh 
artificial heart system will answer some of these questions, but 
within the body we must continue to think in terms of inter- 

Recently Dr. Henry S. Simms, of Columbia University, has 
made an important study which indicates that both the in- 
creasing debility and the increasing death rate that are mani- 
festations of senescence are the result of the same general 
physiological alterations. More than a century ago, Gom- 
pertz declared that after the age of thirty-five the probability 
of death increases with increasing age in geometrical progres- 

12 Cowdry, E. V. "We Grow Old." Scientific Monthly, Vol. 50, p. 52, 1940. 


sion, like accumulating compound interest. 13 Dr. Simms has 
calculated from the total deaths from all causes reported for 
the year 1936 that the probability of death increases regularly 
8.1 per cent per year. The feature of most interest in his cal- 
culations is that nearly all diseases fall into two clear-cut 
groups, each of which obeys the compound interest law, but 
at different rates. The probability of death from each of the 
cardiovascular and kidney diseases increases about 1 1 per cent 
per year. The other group, in which the probability of death 
increases about 5 per cent per year, includes most infectious 
diseases, digestive diseases, lobar pneumonia, diseases of the 
nervous system which are not vascular in character, respiratory 
diseases (except tuberculosis and bronchopneumonia), goiter, 
pellagra, arthritis, and diseases of the skin and bones— surely 
an extraordinary assemblage of human ailments. Yet since 
the probability of death increases with age similarly for each 
member of this group, their lethality in all probability de- 
pends on some common physiological condition (Q) which 
alters with age. What this may be we have at present no 
inkling, but it is something to have learned that death from 
so wide a variety of causes may be due to a single constitu- 
tional factor. 

For the cardiovascular and renal diseases, much the same 
may be said. Here an additional constitutional factor (R), 
perhaps the elasticity of the arteries or the permeability of 
the capillaries, is involved. If the Q factor is concerned here 
too, as seems probable, the R factor must alter at the rate of 
6 per cent per year. The probability of death from a few other 
diseases, such as cancer and bronchopneumonia, also increases 
with age, but irregularly, not as compound interest. Even the 
increase in senile debility would appear to follow the law. 
"The high death rate in old age is the result of changes which 
make us succumb more readily to all diseases, although the 

13 P t = ^o e fc ', where P t is the probability of death at a given time, t, and P 
is the probability of death at birth, e is the logarithmic base, and k is a 
positive constant (the "interest rate"). 


change is faster for the vascular diseases. Nearly four deaths 
out of five after the age of thirty are due not to a greater 
prevalence of disease but rather to the change in the Q and 
R functions which increases the death rate from the same dis- 
eases which affect young people." 14 

How much more hopeful is such a situation than would 
be the random accumulation of degenerative changes. To 
have one major enemy or two, to seek them out, combat 
them, and overcome them singly— this science has often done. 
We may yet live to see it done again. But who can fight a 
mist, a creeping miasma? 

Whatever such constitutional factors may be, however 
modifiable by environmental circumstance, there is little 
doubt that the genes have much to say in determining them. 
Studies by Karl Pearson in England and by Raymond Pearl 
in the United States indicate that longevity in man is defi- 
nitely influenced by hereditary factors. Pearl, for instance, 
found in the study he made that almost 87 per cent of those 
who lived to a very old age (over ninety) had at least one 
long-lived parent (over seventy), and about an equal propor- 
tion had at least two long-lived grandparents. Any conclu- 
sion as to the degree of importance of heredity here must be 
accepted with due reserve. We should be well aware that not 
only may positive correlations of this type arise from resem- 
blances in genotype but that correspondences in environment 
will also tend to produce them. Thus mortality rates vary 
significantly with income level and hazard of occupation, and 
the death rate among infants of the poor is far greater than 
that among infants of the well-to-do. The potency of he- 
reditary factors in determining longevity must accordingly be 
assessed differently in each of the innumerable varieties of 

i4Simms, Henry S. "Physiological Alterations as the Cause of Senile De- 
bility and Senile Mortality." Science, Vol. 91 ns., pp. 7-9, January 5, 1940. A 
1941 report that the presence of the adreno-cortical hormones in the heart 
tissues is necessary for the normal functioning of the heart and that either 
too much or too little of these over a prolonged period will lead to heart 
failure may possibly be a clue to the nature of the R function. 


circumstance. Pearl performed a series of experiments with 
inbred wild-type and vestigial-winged Drosophila that makes 
the situation clear. Vestigial-winged flies, when raised under 
standard laboratory conditions, have a higher mortality rate 
than flies with normal wings. Their duration of life was, on 
the average, less than half that of the strain of wild flies used. 
However, by increasing the density of the wild-type flies per 
bottle, their life curve could be made to correspond to that 
of vestigial flies; while, under complete starvation, the ves- 
tigial flies equaled the performance of the normal flies, re- 
gardless of the initial density. Clearly, the hereditary factor 
that differentiates vestigial from wild type does not inherently 
determine the length of life. It somehow militates against an 
optimum use of the standard environment by the vestigial- 
winged type. Other experiments have shown that wild popu- 
lations contain numerous genetic factors which similarly vary 
the adaptation to particular environments. Heredity and en- 
vironment must always be considered together. 15 

In most cases the influence of the genes is not negligible. 
What an abundance of lethal and semilethal genes are known 
in those organisms which have been studied genetically! 
Most of those in man produce fatal consequences in early 
development, but there are a number which act later. The 
dominant gene for Huntington's chorea usually manifests 
no effects until after the carrier has attained maturity, and 
often not until the age of thirty-five or forty. Diabetes is 
commonly not manifested until middle age. Hemophilia is 
sometimes not fatal until the victim is well on in life. The 
tendency to develop cancer finds expression, as a rule, only in 
late maturity or old age. Just as plausibly we may assume 
that there are also genes which, either singly or in conjunc- 
tion, are responsible for the breakdown of the circulatory 
system or kidneys. 

15 Pearl, Raymond and Pearl, Ruth D. The Ancestry of the Long-Lived. 
Johns Hopkins Press, Baltimore, 1934. 

Pearl, Raymond. "Experiments on Longevity." Quarterly Review of Biol- 
ogy, Vol. 3, pp. 39!-407» 1928- 


On these questions research into the causes of death of 
identical twins, particularly those who have lived apart for 
some time prior to death, should be highly illuminating. 
There are general rep orts that identical twins frequently 
fall ill of the same diseases and die within weeks or days of 
each other, buTno extensive study has as yet been under- 
j-gV^r ^ Mr^r^f TJTITes of twins sto p short with their history at 
the time of investigation-or at least the twins under obser- 
vation were initially so young that follow-up studies have 
not yet reached the period of their old age and death. 

Some day men may live to the average age of a century. 
First, however, there will have to be an intensive search for 
the genes that make for long life and a laborious exploration 
of the ways in which they produce their effects. Working 
from the environmental side, we may improve our measures 
to ward off disease and accident and to strengthen our re- 
sistance to whatever factors speed up the impairment of our 
vital faculties. But some day we may reach this goal, perhaps 
even in our children's time. Will men be any happier then 
than we are today? If a lengthened life means merely a pro- 
longation of the years of senility and decrepitude, who could 
wish for it? Or is a placid, vegetative existence of a century 
to be prized more highly than a short life and a merry one? 
These are questions of values, and men will judge vari- 
ously. There were Schubert and Keats who matured early 
but died young. There were also Titian and Edison, who 
did some of their best work after they were seventy, men 
who grew greater as they grew wiser in experience, yet re- 
mained eager as youths to learn something new and to ac- 
complish something finer. If most old people lose their 
terror of death as their passions decline and their sensibility 
to pain diminishes, whence so startling a zest for life in 
others? Does it come from their continuing purpose in exist- 
ence? If so, how important for us to plan for our future 
years— not so much for our security as for the continuation 
of useful activities, of vital interests. To keep on growing- 


is this our fountain of youth? Our bodies have differen- 
tiated until with specialization they have lost the capacity to 
grow and even to repair anything more than minor injuries. 
The mind, however, may hold its power to develop, insofar 
as we know, as long as it is fed and exercised. 

Genes alone do not make the man, and our development, 
as it progresses, tends to become more modifiable by environ- 
mental factors. For this reason, as we age we need to devote 
a greater proportion of our energy to conscious direction 
of, and control over, the changes within us, lest we suffer 
the dire consequences of haphazard development. Our great- 
est opportunity to do this undoubtedly lies in the sphere of 
the mind. 

The peril for us lies in the probability that in becoming 
overspecialized for a particular niche in human society we 
may, like our cells and tissues, lose our adaptability. How 
many men, as they retire or are thrust out from lifelong oc- 
cupations, are at a loss what to do with themselves! Yet the 
mind need never be narrowed to occupational interests alone. 
One's occupation should rather be the center of an ever 
broadening sphere of related interests, and one's life, as 
Havelock Ellis urged in The Dance of Life, an art— the great- 
est, indeed, of all the arts—consciously pursued as such, to 
its very end. The world has need of old people, need for their 
wisdom, their guidance, and their experience. But for that 
day when we too shall be old we must plan and prepare 
now, lest our wisdom and skill be found inadequate. 

In the end we shall pass away— as "the grass withereth and 
the flower fadeth." Only those genes that made us, as they 
made our forefathers, cast into ever new combinations in 
the recurrent cycle of sexual reproduction, may live on to 
produce new hands, new eyes, and new minds, to test out 
each variety of environment, to continue our struggle to 
mold a world one step nearer the heart's desire. 


Abdomen, 272, 281, 282 

Abortion, 77 

Absorption, 236, 271 72 

Accident, 212, 349, 355 57» 3 6 9 

Accommodation, 291-92 

Acetylcholine, 327 

Acid, 125, 270; butyric, 62; caibolu, 

350; fatty, 272; hydrochloric, 272; 

lactic, 31; nicotinic, 211, 216; 01- 

ganic, 40, 165, 183, 184, 197; 

pyruvic, 31. See Amino 
Acquired characters, inheritance of, 

Acromegaly, 333 
Actinophrys sol, 122, 123 
Adaptability, 241, 361 
Adaptation, 189-90, 222, 223 
Adjustment. See Response 
Adolescence, 280, 314, 329, 348 
Adrenal gland, 201, 209, 284, 331-32, 

334, 340, 345. See Cortex, adrenal; 

Medulla, adrenal 
Adrenalin, 39, 303, 331 
Adulthood. See Maturity 
Age, 116, 204-05, 216, 356, 357, 362; 

old, 340, 348, 368 
Ageing, 44, 347, 348-49' 357 '7° 
Aggregala eberthi, 15-16 
Albinism, 81-89, 91, 92-93, 98-100, 

168-71, 182, 212 
Albumen, 58 
Alcohol, 11, 189, 217, 350 
Alga, 25, 125, 126, 127, 134, 144, 228, 

231. See Chlorogonium, Codium, 

Pleodorina, Spirogyra, Volvox 
Alkali, 125 
Allantoin, 351 
Allantois, 250-51, 252, 254, 257, 262, 

269, 271, 286, 336 
Allele, 70, 71, 83, 97, 101-03,' 109, 110, 
114, 119, 120, 137, 144, 145-46, i5 8 > 
160, 168, 174, 187, 213; blending, 
88-92, 93, 95, 103, 144-45. 169, 171, 
187, 188; dominant, 79, 82-83, 85, 

92-93. 95' 9 8 "99> i°9' 1 10 ' 144. H5. 
158, 159, 160, 174, 182, 183, 184, 

185, 187, 196, 210, 368; multiple, 79, 
92-98, 109, 187, 188; recessive, 76, 
82-83, 85, 88, 92-93, 94-95' 98-100, 
107, 108, 109, 110, 113, 143, 145' 
158, 159, 174, 181, 185, 196, 198, 
207, 210, 215, 288, 333, 353; segrega- 
tion of, 83-84, 102, 104, 119, 141, 
144, 145, 146, 151, 172; symbols for, 
83, 110 

Allen, E., 201 

Allergy, 260, 261, 352, 353, 354 

Allium cepa, 24 

Alternation of generations, 126-29 

Ameba, 33, 37, 40, 42, 58, 223, 229; 
diploidea, 67 

Amino, acid, 39, 164, 165-67, 216, 238, 
270, 272, 329; base, 196 

Ammonia, 270 

Amnion, 247-49, 251-54, 257; cavity 
of, 237, 247; fluid of, 248, 252 

Amphiaster, 21, 36 

Amphibian, 62, 140, 194, 251, 257, 
267, 278, 285, 295, 296, 298, 311. 
See Frog, Salamander, Toad 

Amphioxus, 223, 257, 284 

Anabolism, 164 

Anaphase. See Mitosis 

Ancestry, 69-70, 88 

Angiosperm, 58, 62 

Animal, asymmetry in, 209-10; cell 
division in, 12, 24, 33; development 
in, 235, 239-41, 243-46, 248, 251, 
254, 257, 333, 358; fertilization in, 
60-63; gametes of, 53-60, 125, 130- 
33; land, 315, 344; life cycle of, 
128, 129; meiosis in, 64-66; poikilo- 
thermic, 361; sex in, 121, 135-36. 
138, 141, 147-62. See Invertebrate, 
Protozoa, Vertebrate 
Ankle. See Limbs 

Annelid, 137. See Worm, segmented 
Ant, 129, 205, 206, 232 
Anthocyanin, 175, 183-84 
Anthoxanthin, 183, 184 
Anthrax, 351, 353 
Antibody, 93-97, 353"55 

37 1 



Antigen, 93-97, 261, 354 

Antiseptic, 350 

Anus, 253, 254, 268, 269, 271, 287, 337 

Anvil. See Bone 

Aorta, 262-63, 265-67, 268 

Aortic arch, 262, 263-67, 277, 278 

Ape, 259, 301, 308, 316, 324, 347 

Apotettix, 106 

Appendicitis, 350, 355 

Appendix, 269, 271 

Aristotle, 2, 49 

Arm. See Limbs 

Artery, 250, 256, 262, 263, 282, 361, 
365, 366; pulmonary, 267, 278. See 
Aorta; blood, vessel 

Arthritis, 366 

Arthropod, 74. See Crustacea, Insect 

Ascaris, 14, 15, 223, 248. See Round- 

Ascomycetes, 67 

Association. See Cerebral hemisphere, 
Nerve, cell 

Assortment. See Chromosome, Gene 

Aster, 12, 21, 22, 24, 31, 33, 35, 36, 

37' 6 2 
Asymmetry, 209-10, 216 
Atrium, 266. See Heart 
Auditory. See Ear, Nerve 
Auricle, 267, 268. See Heart 
Autocatalysis, 7, 26, 33, 42-43- l6 3 
Autonomic. See Nervous system 
Autosome, 152, 153, 156, 158. See 

Auxin, 38-39, 197-98 
Average, 179-80. See Mean 
Axis. See Symmetry 
Axolotl, 29 

Baboon, 204, 205 

Baby, 203, 275, 282, 292, 293, 296, 309, 
330, 348; "blue," 268; mortality, 

348, 349 
Back, 304, 306, 307 
Backbone, 255, 282, 306-07, 308, 309, 

312. See Vertebra 
Bacteria, 4, 5, 13, 42, 60, 211, 260, 279, 

280, 349, 350, 351, 352. See Disease 
Bacteriophage, 5-7. See Virus 
Balancer, 194 
Bat, 129 

Bateson, William, 81 
Bean, 122; mutant, 72, 137, 143 
Becker, Carl, 233 
Bee, 15, 81, 129, 205, 232 
Beech, 138 
Belaf, 15, 20 
Bell, Sir Charles, 315 
Beriberi, 351 

Bile, 270, 271, 273, 328 

Binomial expression, 177 

Birch, 138 

Bird, 62, 234, 236, 238, 242, 248, 250, 
257, 261, 267, 273, 281, 311, 321, 
338, 362; sperm (Chloris), 57; sex 
in, 156, 199, 200. See Chicken 

Birth, 232-33, 261, 264, 267, 278, 281, 
287, 309, 314, 315, 330, 332, 340, 
346, 347, 348 

Bladder, gall, 269, 270, 271, 274, 328; 
swim, 257; urinary, 211, 250, 251, 
271, 286, 287, 303, 336 

Blastocyst, 237 

Blastula, 230-31, 234, 235, 236, 239 

Blindness, 293; color, 158-60, 212; 
night, 196 

Blood, 195, 211, 237, 238, 243, 250-52, 
255, 256, 260-72, 275, 277-79, 283-86, 
326, 328, 329, 331-33- 342, 343» 344> 
353' 362; clotting, 260-61, 331; 
groups, 94-97, 354; homeostasis, 361; 
islands, 260; plasma, 362, 363; 
poisoning, 350; pressure, 331, 332; 
proteins, 260-61; red cells, 10, 94, 
237, 260-61, 270, 313, 362; serum, 
38, 94, 96, 363; transfusion, 94; ves- 
sel, 211, 243, 250, 255, 256, 260, 
262-65, 276, 291, 293, 303, 313, 342, 
35 1 > 365; white cells, 37, 38, 211, 
232, 260, 270, 313. See Antibody, 

Body, cavity, 254, 335; pattern, 190- 
211; proportions, 202, 203, 205, 206, 
207, 208; size, 332-34; stalk, 247, 
248, 249, 252, 253, 254, 262. See 
Coelom; Form; Segment, meso- 

Bone, 202, 210, 243, 255, 257, 261, 294, 
295-9 6 ' 3°2, 3°5-°7' 3°8-i6, 328, 329, 
333' 359' 364. 3 66 : anvi1 ' 2 94' 296. 
309; breastbone (sternum), 282, 311, 
312, 313; clavicle (collarbone), 312; 
coracoid, 312; femur, 315; fibula, 
315; hammer, 294, 296, 309; hu- 
merus, 312, 313; hyoid, 310; mar- 
row cavity, 314, 315; mastoid 
process, 296; radius, 313; red mar- 
row, 261, 313; rib, 282, 307, 310, 
311, 312; sacrum, 308, 311; scapula, 
312; stirrup, 294, 296, 299, 300, 309, 
310; tibia, 315; ulna, 313; yellow 
marrow, 313. See Backbone, Cra- 
nium, Skeleton, Skull, Vertebra 

Bonellia, 136 

Boveri, 14 

Brachydactyly, 333 

Brain, 194, 195, 209, 210, 241, 242, 



245, 246, 255, 256, 258, 269, 277, 
289, 293, 297, 300, 316-26, 327, 365; 

hemorrhage, 261; olfactory lobe, 
323; -stem, 210, 320, 324. See Cere- 
bellum, Cerebral hemisphere, Me- 
dulla, Pons, Thalamus 

Breast, 341, 346; nipple, 303. See 
Mammary gland 

Breastbone. See Bone 

Breathing, 281-82, 330. See Respira- 

Bridges, C. B., 112 

Bronchus, bronchial tube, 278, 279, 

Bryophyte. See Liverwort, Moss 

Bubonic plague, 349, 350, 351 

Bud (rudiment), 182, 194, 196, 198, 
199, 241, 257, 271, 273, 285, 303, 
304-05; taste, 288 

Bug, 14, 29. See Lygaeus, Protenor, 

Bursa, 174 

Biitschli, 12, 13 

Butterfly, 156 

Caecum, 269, 271 

Calcium, 216, 275, 307, 328, 329, 330, 

Canal, cochlear, 300; hyaloid, 291, 
292; semicircular, 297, 298; tym- 
panic, 299, 300; vestibular, 299, 300 

Cancer, 15, 38, 351, 352, 353, 354* 356, 
357, 366, 368 

Cantaloupe, 359 

Capillary, 250, 263, 272, 278, 282, 284, 
285, 302, 366. See Blood, vessel 

Carbohydrate, 59, 164, 270. See Food 

Carbon dioxide, 28, 36, 39, 40, 238, 
248, 265, 266, 270, 278, 279, 283 

Carbon monoxide, 41 

Carboxyl, 165 

Cardiovascular disease, 352, 357, 366- 

Carrel, Alexis, 44, 362; and Lindbergh, 

3 6 5 

Cartilage, 243, 257, 265, 278, 280, 295, 
302, 305-07, 308-15, 364 

Casein, 60 

Castle, W. E. and J. C. Phillips, 181-82 

Castration, 199, 200 

Cat, 223 

Catabolism, 164 

Catalysis, 166, 186. See Autocatalysis 

Cattle, 75-76, 155, 343; bulldog, 76, 
91; Dexter, 91; freemartin, 199 

Cell, 90, 169, 181, 190, 191, 192, 193, 
233, 271, 353; aggregation, 47; ame- 
boid, 32; differentiation, 32, 44, 45, 

47, 131, 163, 182-83, 193, 221, 225, 
228, 229, 231, 235, 240, 241, 244, 
245, 285, 289, 305, 306, 361 (See 
Differentiation, Specialization); divi- 
sion (See Mitosis); enlargement of, 
38, 197-98, 291; fragment, 10; hair, 
288, 297, 299, 300; isolation of, 124, 
227; layers, 235, 243; migration, 
200, 221, 232, 270, 304, 306, 307, 
326, 331; muscle, 241, 244, 246, 303, 
304; number, 221; plant, 229; plate, 
31; shape, 229; size, 33, 54, 182, 
226; somatic (vegetative), 11, 45, 
149, 228, 231; spherical shape, 32; 
stinging, 240; surface, 228-30; 
theory, 7-9; volume, 33, 40, 228-30, 
304; wall, 25. See Blood, red cells, 
white cells; Diploid; Epithelium, 
cells; Excretion, cells; Haploid; 
Nerve, cell; Reproduction, cell; 
Sex, cell; Triploid 

Cellulose, 25, 31 

Centrifuge, 34, 35; ultra-, 5-6 

Centriole, 21, 22, 34, 55 

Centromere, 29, 34, 116 

Centrosome, 20, 21, 23, 24, 25, 29, 33- 
34, 36, 55, 62 

Cerebellum, 321, 323, 326 

Cerebral hemisphere (cerebrum), 320, 
321, 322, 323, 324, 325 

Chambers, R., 37 

Chance, 60-61, 70, 80, 101, 102, 103, 
104, 153, 186, 355 

Character, acquired, 11, 222; second- 
ary sexual, 200-01. See Trait 

Chemical, attraction, 60; correlation, 
328-34; reaction, 164, 185-87, 188, 
356. See Synthesis 

Chest, 207, 272, 280-82, 304, 306, 307, 

Chestnut, 138; horse, 137-38 

Chiasma, 111, 112 

Chicken, 44, 49, 174, 223, 236, 338; 
Andalusian, 91; bantam, 333; rump- 
less, 212; White Leghorn, 170; 
White Silkie, 170 

Childhood, 329, 340, 347, 348 

Chilomonas, 40, 42 

Chin, cleft, 310 

Chloride, 332 

Chlorine, 216 

Chlorogonium, 45, 124, 125. See Alga 

Chloroplast, 45, 230 

Cholera, 349 

Chondriosome, 31, 60 

Chordate, 223, 256, 304. See Amphi- 
oxus, Vertebrate 

Chorion, 247, 248, 250-53, 254 



Chromatid, 65 

Chromatin, 14, 20, 22, 28 

Chromonema, 26, 28 

Chromosome, 18, 23, 24, 34, 55; ab- 
normal, 17; assortment and recom- 
bination of, 64-71, 80, 98, 102-06, 

117, 153; behavior during meiosis, 
64-70, 102, 118; behavior during 
mitosis, 20-22, 25-31; deficiency, 79, 
168; discovery of, 12-13; disjunction, 
27-30, 36, 64-71, 83, 104; duplica- 
tion (reproduction), 25-27, 33, 43, 
64-66, 118-19, 225; effects of x-rays 
on, 17; form, 16-19, 27-28, 147, 148; 
homologous, 63, 65-68, 70, 83, 104, 
109, 110, 111, 112, 120, 146, 147, 
150, 161; matrix, 26, 28; mapping, 
112, 113, 116; number, 14-15, 105; 
pairing (See Synapsis); persistent 
individuality of, 14-19; reduction, 
64, 80; salivary gland, 17, 18, 79, 

118, 168; segregation, 64-69, 120, 
1 S^» 153. 154. 161; sex, 110, 146, 
147-57. !57- 6 2> 181, 334 {See X- 
chromosome, Y-chromosome); size, 
16, 117, 148-49, 158; theory of hered- 
ity, 65, 103-04, 109. See Crossing 
over, Gene, Linkage, Nondisjunc- 
tion, Synapsis 

Cilia, 55, 57, 58-60, 244, 245, 279, 288, 

297, 298, 300. See Cell, hair 
Ciliate, 58, 134. See Paramecium 
Circulation, 248, 256, 259-68, 270, 326, 

329, 368 
Clavicle. See Bone 
Cleavage, 31, 36, 132, 224-29, 234; 

furrow, 36-37 
Cleopatra, 143 

Climate, 11, 189, 276, 303, 340, 353 
Clitoris, 337, 339, 344; glans of, 339 
Cloaca, 250, 251, 255, 269, 283, 286, 

Clone, 43 
Coagulation, 36 
Coccyx, 308, 311. See Tail 
Cochlea, 294, 298, 299, 300 
Codium, 140-41 
Coelenterate, 129, 137, 239 
Coelom, 247, 248, 281, 283, 284, 286 
Coitus, 344 
Colchicine, 27, 28 
Cold, 359; sense of, 288; (disease), 351, 

Cole, F. J., 49 
Colloid, 5, 9, 32, 164, 260, 360, 361. 

See Gel, Sol 
Color, 289, 291; eye, 81-82, 92, 109-10, 

113-15, 169-70, 181, 185, 187, 188, 

196-97; egg, 189; fat, 164; feather, 
91; flower, 88-90, 105, 175, 176, 183- 
84, 186; hair, 81-82, 92-93, 98-100, 
181, 182; larval, 189; skin, 81-82, 85, 
91, 170-75, 176, 181. See Albinism; 
Blindness, color; Pigment 

Colostrum, 355 

Concentration, auxin, 197; change, 
31, 186: enzyme, 184-85; gradient, 
193, 279; hydrogen ion (See pH); 
osmotic, 36. See Response, maxi- 
mum; Threshold 

Conjugation, 42, 67, 122, 126, 134 

Connective tissue, 243, 276, 288, 296. 
302, 303, 305, 306, 317, 335, 336, 
364; fibers, 210, 292, 293, 306; fibro- 
blast, 363 

Constitutional, difference, 352, 357; 
factor, 366, 367 

Convection, 230 

Coordination, 225, 231, 240, 260, 316- 
27; chemical, 328-34. See Integra- 

Copper, 40, 216 

Cornea, 292, 293. See Eye 

Corona radiata, 59 

Corpus callosum, 322, 323 

Corpus luteum, 342, 343, 345 

Corpus striatum, 322 

Correns, 81 

Cortex, adrenal, 201, 331, 332, 334, 
340, 345, 366; cerebral, 323; gonadal, 

198, 199 
Cortin, 331, 332, 340 
Cousin-marriage, 142-43 
Cowdry, E. V., 361 
Crab. See Inachus 
Cranium, 308, 332 
Crayfish (Cambarus), 14 
Crepidula, 15, 139 
Cretinism, 213, 329 
Criminality, 217-18 
Crocodila, 267 
Cross, 86, 92, 105, 106, 141; (dihy- 

brid), 98-102, 170; interspecific, 189; 

(monohybrid), 83-85, 88-89; test> 

(back-), 87, 90, 99, 101, 107-09, 110, 

113; three-point, 113; (trihybrid), 

Crossbreeding, 69, 141, 144, 157 
Crossing over, 103,. 107-20, 146, 162. 

181; double, 114-15; frequency of, 

Crustacea, 55, 129, 304 
Cucumber, 138 

Cutleria-Aglaozonia, 127. See Alga 
Cycad, 55, 58; sperm (Zamia), 57 
Cyst, 125, 126, 275, 359 



Cystine (cysteine), 39, 41, 52, 216 
Cytoplasm, 20-21, 44» 55> 57 » 59- 6o > 
65, 125, 126, 132, 156, 163, 191, 195, 
225, 226, 228, 230, 317, 355; divi- 
sion of, 22, 24-25, 30-31, 36-37, 42; 
gelatin, 35-36; and gene products, 

Daphnia, 360 

Darwin, 13, 222 

Datura, 106 

Davenport, 172 

Deafness, congenital, 174-75 

Death, 42, 44-45, 232-33; causes of, 
348-70; rate, 155, 349- 35°. 3 6 5" 68 

Dentine. See Tooth 

Dentition. See Tooth 

Dermis, 302, 303 

Desmid, 42, 58, 126 

Development (ontogeny), 1-2, 8, 12, 
13, 132, 162, 163-220, 221-347, 364; 
requisites for, 9-10 

Deviation, non-random, 179; stand- 
ard, 179 

DeVries, 81 

Diabetes, 351, 353, 356, 368 

Diaphragm, 281, 282, 325, 327 

Diarrhea, 349 

Diatom, 42, 58, 126, 134 

Diet, 180, 189, 205. See Food, Nutri- 

Differentiation, 44, 47, 167, 193, 198, 
359, 361, 364, 370; sexual, 133-37 

Diffusion, 230, 279 

Digestion, 164, 165, 235, 236, 240, 241, 
259, 260, 268-77, 365; cavity, 235, 
240, 242, 245, 303; diseases of, 366; 
tube (gut), 249, 253, 254, 265, 268, 
271, 275, 284 

Digit, 259, 288, 305, 311, 315, 3 l6 > 334 

Dioecious, 141, 146 

Diphtheria, 349, 351, 353, 35 6 ; ana- 
toxin, 355, 356 

Diploid(y), 64, 67, 71, 92, 104, 121, 
124, 126, 127, 128, 129, 130, 131, 
i33» 136-40, 145. H7> x 48, i5 x > x 52, 
153, 154, 156, 157, 162, 225 

Disease, 332, 338, 348, 349'57> 3 66 - 
367, 369; susceptibility, resistance 
to, 179, 214, 260, 352-56, 357. See 
Man, hereditary disease; Cancer, 
Diabetes, Tuberculosis, etc. 

Distribution, bimodal, 178; normal 
frequency, 177-79; of substances, 
229-31, 240, 242-46, 259-68 
District, 193, 194, 201, 208, 209 
Division of labor, 45, 54, 120, 167, 
221, 224-25, 228, 231, 232, 240 

Dog, 170, an, 343» 345» 362-63; basset 
hound, 207; dachshund, 207; mas- 
tiff, 333; Pekingese, 333; St. Ber- 
nard, 333 

Dominance, 82, 83, 88-89, 90, 92-93, 
95, 98, 101, 102, 103, 161, 168, 170, 
174, 175, 184, 185-88, 193, 208-09. 
See Allele 

Drosophila, Bar, 83, 109-10, ill, 213- 
14; black, 113-15; bobbed, 160; car- 
nation, 109-10, 112; chromosomes, 
15, 16, 17, 18, 27, 28, 117, 147-54, 
161, 168; cinnabar, 196; crossing 
over, 109-15, 117; diffusible gene 
products, 181; dumpy, oblique, vor- 
tex, 97-98; hormones, 195-97; inter- 
sexes, 156, 157; linkage groups, 105; 
multiple alleles, 92, 187, 188; mu- 
tants, 73, 97-98; mutation in, 74-75, 
77, 79; purple, 113-15; recombina- 
tion, 106-07; scarlet, 196; sex deter- 
mination, 147-54; sex-limited in- 
heritance, 160; sex-linkage, 158; 
transplantation, 182; vermilion, 
196; vestigial, 113-15, 368; white 
eosin, 188; yellow, 185. See Hybrid, 
Intersex, Nondisjunction 

Dublin, L. I., 348 

Duct, bile, 270; endolymphatic, 297; 
excretory, 255, 256, 283, 284, 285, 

286, 287, 335; lymph, 272; pancre- 
atic, 271; sexual, 200-01, 246, 284, 

287, 336-37' 339. 340, 344 
Dunn, L. C, 160 
Dutrochet, 7 

Dwarf, 333, 334. See Cretinism, 

Dysentery, 349 

Ear, 194, 257, 258, 273, 275, 293-01, 
321, 322, 325, 326; bones, 294, 295- 
96, 299; -drum, 294, 296, 309; oto- 
liths, 297, 299. See Canal, Cochlea, 
Hearing, Sacculus, Utriculus 
Earthworm (Lumbricus) , 122, 138, 

223, 255, 256 
Ectoderm, 192-95, 235-38, 239-41, 242- 

47, 248, 289, 293, 301, 316, 326 
Educational achievement, 218 
Egg (ovum), 10-12, 24, 32, 34, 35, 49> 
50, 54, 58, 59-63. 64, 65, 68, 82, 84, 
98, 100, 103, 121, 125, 127, 129, 130, 
132, 133. !34> *44> x 45> !47> x 4 8 ' 
150, 151, 152, 153, 154. 155' !56- 
189, 192, 210, 225, 226, 227, 229, 
241, 246, 251, 339, 341. 342, 346, 
347- 355; bird ' 59' 234-35. 236, 249; 
fish, 249; frog, 234, 249; human, 

37 6 


56; mammalian, 59, 60, 191; num- 
ber, 336; reptile, 249, shell of, 345 

Ehrlich, Paul, 350, 354 

Elbow. See Limbs 

Electric energy, 39, 40, 125, 191 

Ellis, Havelock, 370 

Embryo, 59, 182, 192, 193, 234-35, 362; 
division of, 44; embryonic disk, 237.. 
238, 254; human, 2, 155, 226-28, 
229-30, 236-38, 242-43, 246-52, 253, 
254, 255, 256, 257-340, 345, 346; 
mammalian, 260, 346; membranes 
of, 246-52; monsters, 207, 208, 227; 
sack, 62, 132 

Emotion, 323-24, 354 

Enamel. See Tooth 

Endocrine gland, 198, 323, 328-34, 
338, 346, 365. See Adrenal, Pitui- 
tary, Thyroid, etc. 

Endoderm, 235-38, 239-41, 242-46, 
247, 248, 260, 271, 283 

Endolymphatic sack, 297, 298 

Endomixis, 361 

Endosperm, 62, 107, 130, 132, 133, 184 

Energy relations, 163, 164, 166, 270, 

Enteritis, 349 

Environment, 2, 43, 44, 53, 136, 141, 
161, 178, 180, 187, 189-90, 191, 195, 
198, 205, 222, 227, 230, 235, 240, 
241, 261, 287, 288; and heredity, 
162-64, 211-20, 225, 352-57' 3 6l > 3 6 7" 
70; internal, 136, 180, 189, 195, 215; 
prenatal, 354 

Enzyme, 7, 41, 166-68, 184, 186, 192, 
196, 225, 305; digestive, 236, 241, 
271, 272, 276 

Ephestia, 189, 196-97 

Epidermis, 195, 301, 302, 303 

Epididymis, 339, 341, 344 

Epigenesis, 49-50 

Epiglottis, 279, 280 

Epilepsy, 357 

Epiphyses, 314 

Epistasis. See Precedence 

Epithelium, 261, 273; cells, 301, 302 

Equilibrium, 193, 281, 288, 297-98, 
299, 326 

Equisetum, 136 

Eskimo, 353 

Esophagus, 269, 273, 274, 325 

Ether, 28 

Eugenics, 212, 214 

Eustachian tube, 273, 294, 296 

Evening primrose. See Oenothera 

Evolution, 11, 13, 42, 106, 120, 128, 
136, 146, 147, 156, 157, 161, 189. 

Excretion, 229, 231, 240, 242-52, 257, 
260, 270, 282-87, 361, 362; excretory 
cell, 244, 245, 246; excretory tubule, 
244, 255, 256, 283, 284, 285, 286, 
339; globule, 244 

Eye, 182, 194-95, 196, 212-14, 221, 
243, 244, 245, 257, 259, 288, 289-93, 
321, 325, 329, 365; aqueous humor 
of, 292, 293; choroid layer, 292, 293; 
conjunctiva, 292; cornea, 292, 293; 
iris, 169, 181, 291, 292, 293; lens, 
194, 289, 290, 291, 292, 293; mus- 
cles, 292, 304; pupil, 291, 292; retina, 
289, 290, 291, 292, 293; rods and 
cones, 289; sclera, 292, 293; socket, 
310; vitreous humor of, 291, 292. 
See Albinism, Blindness, Color 

Face, 204, 205, 209, 259, 304, 309, 333 
Factor, genetic, 129, 135, 136, 212, 

288; multiple, 175-80, 333. See 

Fallopian tube, 61, 236. See Oviduct 
Family, 344 
Fat, 59, 164, 216, 271, 272, 303, 313, 

330, 334, 364 

Fatigue, 356 

Feather, 235 

Feeble-mindedness, 178 

Female, 113, 120, 121-22, 130-33, 133- 
38, 138-46, 147-59, l6 2, 198-201, 205, 
254, 284, 287, 334-46, 348, 357, 358, 
360; super-, 150, 151, 152 

Fern, 55, 57, 127, 137; sperm (Mar- 
silia), 57 

Fertility, 74-75, 160, 222 

Fertilizin, 62 

Fertilization, 53, 60-63, 12 5, 133, 148. 
150, 152, 155, 342, 344; cross-, 122, 
141; double, 62; randomness, 60-61, 
70, 80, 153; self-, 122, 128, 139, 141 - 

Fetus, 200, 294, 296. See Embryo. 

Fiber, mantle, 21; spindle, 22, 29. See 

Muscle, Nerve 
Field, gradient, 192-94, 201, 208 
Fin, 257 

Finger. See Digit 
Fish, 139, 156, 249, 251, 257, 265, 279, 

285, 295, 296, 298, 320, 324, 344; 

dog-, 223; lobe-finned, 311; lung-, 

266, 267, 278; sun-, 206, 207 
Fission, 31, 37, 40, 42, 43, 122 
Fitzpatrick, F. L., 351 
Flagella, 45, 55, 58, 230, 241 
Flagellate, 134 


Flatworm, 137, 243-46, 291. See Pla- 
nar ia 

Flea, 350 

Flemming, 12, 13 

Flower, 122, 132, 137-38, i4*> i75"7 6 - 
See Color, Pigment, Plant 

Fly, 351. See Drosophila, Sciara 

Fol, 12, 13, 63 

Follicle, 302, 336, 339, 341, 342, 343 

Food, 10, 33, 42, 45> 54' 5 8 > 59> 6 3> 6 5> 
123, 125, 131, 132, 136, 165, 166, 
225, 226, 229, 238, 241, 248, 250, 
251, 260, 263, 269, 272, 280, 303, 
344; -getting, 240. See Diet, Nutri- 

Foot, 221, 288, 305, 306, 311, 312, 315, 
316, 333; congenital absence of, 76. 

77' 7 8 
Form, 191-92; determination of, 194, 

201-10, 221, 229; development of, 

Four o'clock. See Mirabilis jalapa 
Freemartin. See Cattle 
Frog, 129, 191, 192, 223, 234, 236, 242, 

249, 257, 267, 281, 311, 344 
Fruit fly. See Drosophila 
Fucus, 60; sperm, 57 
Funaria, 136-37, 139 
Fundulus, 15 
Fungus, 67, 135, 144 

Gamete, 47, 53-64, 64-70, 80, 83, 84, 
89, 9°' 95' 96' 97' 98' 99' 10 °' 101 > 
103, 107, 108, 115, 117, 121, 122, 
124-29, 130, 134, 135, 139' x 42, 144, 
145, 153, 171-73; formation, 130-33; 
frequencies, 109. See Egg, Sperm, 
Gametophyte, 127, 128, 132 
Gammarus Chevreuxi, 185 
Ganglion, 245, 317, 3 l8 ' 320, 326, 3 2 7 
Gastrovascular cavity, 239, 240 
Gastrula, 234-36, 238, 239, 240, 242, 


Gates, R. R., 77 

Gel, 9, 21, 32, 35-36 

Gene, 8-12, 18, 44, 47, 53' 54. 61, 63. 
77, 232, 233, 355, 35 6 ' 357'' auton- 
omy of, 180-82; biochemical action, 
169-71, 175, 183-88, 198, 213; com- 
mon to related species, 222-23, sir- 
complementary, 174-75; complexes, 
10, 136, 222; deficiency, 185; defini- 
tion of, 79, 82, 118, 222; dosage, 
184, 187; duplicate, 174; duplica- 
tion of, 19, 26-27, 29, 33, 43' 8o ' 
human, 82, 158, 249, 368; inde- 
pendent (random) assortment of, 

98-103, 104, 105-06, 116, 117, 142, 

146; interaction, 103, 167-80, 353; 
lethal, 75-77, 79' 9*'92, *43> 333' 
368; linear seriation, 116, 118; lo- 
cus, 26, 112, 114; maps, 112, 116; 
modifying, 170, 187; mutant, 2^, 
i0$, iro> it& 12-8, 3.ifJ; number of, 
69; parallel behavior with chromo- 
somes, 102-06, 109-12; potency, 187, 
213; products, 180-90, 192, 228; re- 
combination, 68, 80-103, 107-20, 
141, 146, 151, 161, 172, 178; regu- 
lation of development, 167-90, 192, 
195-98, 201, 205, 207-08, 219-20, 225, 
249, 288, 305, 333, 334' 347' 367-7 o ; 
sex, 135-38, 139, 140-4 1 ' 144-4 6 ' *47- 
57; sex-linked, 157-62; stability of, 
74, 78, 86, 89-90; string, 27, 28; 
subject to natural selection, 222; 
symbols, 83. See Allele, Crossing 
over, Linkage, Mutation 
Genetic continuity, 11-14 
Genetics, human, 352 
Genitalia, 200, 201, 337-38, 339-41 
Genotype, 83-85, 89, 90, 95, 96, 97, 98, 
QQ-101, 102, 108, 136, 138, 142, 144, 
145, 164, 169, 182, 185, 186, 188, 
189, 199, 201, 212-15, 219, 352, 354, 
361, 367 
Genotypic ratio, 85, 89, 90, 98 
Germ, 275, 296, 349, 350. See Bac- 
teria, Virus 
Gigantism, 209, 332-33 
Gill, 194, 265, 278, 279, 294; arch, 
309; bar, 278, 295, 296, 310; cleft 
(furrow), 249, 257, 258, 265, 274, 
278, 294, 295; muscle, 304; pouch 
(See Pharynx, pouch); slit, 257 
Ginkgo, 55 

Gland, 289, 317, 325' 328-34, 34 1 ! 
cells, 241, 244, 271, 272, 276, 285, 
302, 316; gastric, 272; intestinal, 
271; lymph, 275; oil, 235; shell. 
246; skin, 301-03; sweat, 235, 302, 
303; tear, 325; yolk, 246. See Ad- 
renal, Endocrine, Mammary, Pan- 
creas, Parathyroid, Pituitary, Pros- 
tate, Salivary, Thymus, Thyroid 
Globulin, 35-36 
Glucose, 59. See Sugar 
Glutathione, 39, 40, 41, 186; structure 

of, 52; tests for, 52 
Glycerin, 272 
Glycogen, 59, 269, 271 
Goiter, 211, 328, 329, 330, 366 
Gompertz, 365 

Gonad, 287, 335-36' 338. See Repro- 
duction, organs of; Ovary; Testis 



Gonorrhea, 293, 350 

Gourd, 208 

Gradient, axial, 193, 194, 209; elec- 
tric, 209; growth, 205-07, 209, 210; 
metabolic, 191, 192. See Concentra- 
tion, gradient; District; Field; Sym- 

Graft, 194, 199 

Gramicidin, 351 

Grasshopper (locust), 15. See Apot- 
tetix, Stenobothrus 

Gravity, 192, 197, 299 

Gray, James, 35, 38 

Gregarine, 126; gametes of, 54 

Growth, 1-2, 65, 131, 132, 163-220, 
221, 226, 253, 275, 314, 320, 330, 
336, 340, 359; beginning of, 229-34; 
center, 205-07, 209; gene-controlled, 
186, 207-08; hormones, 332-34, 345 
(See Auxin); primary and second- 
ary, 38; rate of, 362, 363, 364; rela- 
tive rates, 201-10, 259; requisites 
for, 9-10. See Gradient, growth; 

Guinea pig, 98-101, 182, 345, 346 

Guppy. See Lebistes 

Gut. See Digestion, tube 

Gymnosperm, 57 

Gynandromorph, 181 

Habit, 319 

Habrobracon, 196 

Hair, 209, 235, 257, 301, 302, 365; 
beard, 340, 341; hairlessness, 41; 
rough vs. smooth, 98-101; woolly, 
73, 76. See Albinism; Color, hair 

Hammer. See Bone 

Hammett, F. S., 41-42 

Hand, 221, 288, 305, 306, 311, 313, 
315, 316, 333; congenital absence 
of, 76, 77, 78. See Left-handedness 

Haploid(y), 64, 66, 67, 71, 103, 105, 
106, 117, 122, 123, 124, 125, 126, 
127, 128, 129, 130, 131, 132, 133, 
136-40, 144, 146, 148, 152, 153, 154, 

157' 158 

Harelip, 76, 310 

Hartmann, M., 134 

Harvey, 49 

Hawk weed. See Hierachim 

Head, 191, 193, 202, 205, 206, 207, 
216, 241, 242, 243, 246, 253, 255, 
359> 262, 264, 297, 299, 306, 307, 
310, 333; of sperm, 54-55, 61, 63 

Hearing, 174, 288, 294-96, 298-301, 
322, 324, 325, 365. See Ear 

Heart, 194, 209, 210, 243, 248, 249, 255, 
256, 258, 262, 263, 264, 265-68, 278- 

79> 321, 325. 333» 365; -beat, 326, 
329, 331; disease of, 351, 352, 357, 
366-67, 368; muscle cells, 304; par- 
tition, 266-68; pericardium, 269; 
valve, 266-67, 268 
Heat, 40, 350; sense of, 288; (sexual), 


Height. See Stature 

Heilbrunn, L. V., 38 

Hemoglobin, 260, 270 

Hemophilia, 76, 158, 187, 196, 214. 

Heredity, 1, 2, 8, 11-14, l 9> 43- 64, 69, 
70, 92, 167, 172, 180, 186, 352; chro- 
mosome theory of, 65, 103-04, 109; 
cytoplasmic, 188-90; and environ- 
ment, 162-64, 211-20, 225, 352-57, 
361, 367-70; maternal, 188-90, 354- 
55; Mendelian laws of, 87, 100-03, 
104, 118, 172; pattern of, 1-2, 80- 
10 3> x 57' ^2, 214, 225, 227, 233, 
251- 3*9* 324 

Hermaphroditism, 122, 135, 138, 141, 
246, 254, 338, 340 

Herrick, C. J., 323-24 

Hertwig, Oskar, 12, 13, 14, 63, 103 

Heterogony, 202, 203-10. See Growth, 
relative rates 

Heterozygosity, 84-87, 89-91, 97-98, 
107-09, 110, 112, 113, 137, 141-43, 
144, 169, 179, 181. See Allele, Gene 

Hieraciiun, 81 

Hog, Duroc-Jersey, 174 

Homeostasis, 361 

Homologue. See Chromosome, ho- 

Homology, 223, 311 

Homozygosity, 84-87, 89-92, 107-09, 
137, 138, 140, 141-43, 154, 168, 169, 
181, 185, 246. See Allele, Gene 

Hookworm, 349, 350 

Hopkins, 52 

Hormone, 6, 38, 39, 181, 192-201, 208, 
315, 328-34, 366; molting, 195; sex, 
198-201, 209, 338-43, 345-46. See 
Auxin, Cortin, Insulin, Organizer, 
Secretin, Thyroxin 

Horse, 355, 358 

Horsetail. See Equisetum 

Horwood, M. P., 349 

Hoskins, 346 

Huntington's chorea, 76, 214, 368 

Huxley, J., 210; and G. R. De Beer. 
201. See Wells, Huxley, and Wells 

Hybrid, 84, 89, 90, 92, 100, 156, 172, 
173, 176, 189; sterility, 27/156-57. 
See Heterozygosity 


Hydra, 44, 138, 223, 239-41, 243, 245, 

Hydrogen, 39, 165; sulfide, 28 
Hydrogen ion, 183. See pH 
Hydroid, 208 
Hydrolysis, 164, 165, 166 
Hydroxyl, 165, 183 
Hypertrophy, 211, 330 
Hypophysis. See Pituitary gland 

Identical sibs, 44, 227, 353, 369 
litis, H., 81 

Immunity, 261, 352; acquired (pas- 
sive), 351, 354-55^ active, 351, 355 
Implantation, embryonic, 238, 342, 


Inachus, sperm, 57 

Inbreeding, 69, 77, 87-88, 98, 141-43' 

Indian corn. See Maize 

Individuality, 70, 231-34 

Infantile paralysis, 5, 351 

Influenza, 6, 351, 355, 357 

Infusoria, 58 

Inheritance. See Heredity 

Insanity, 351, 352, 354, 357 

Insect, 62, 129, 135, 139, 141. 181, 
304, 319. See Ant, Bug, Drosophila, 

Instinct, 232, 319 

Insulin, 39, 271, 328, 334, 346, 356 

Integration, 190-211, 221 

Intelligence, 175, 178, 179, 216, 218, 
316, 323, 324, 333' 334 

Interference, 115 

Interphase, 14, 15, 16, 20, 22, 24, 27, 
28, 41, 63. See Mitosis 

Intersex. See Sex 

Intestine, 209, 210, 250, 270-72, 303, 
325, 328, 335; colon, 269; duode- 
num, 274; rectum, 269, 286, 287 

Invagination, 234, 235, 239, 240 

Invertebrate, 129, 139, 181. See In- 
sect, Worm 

Iodine, 211, 213, 214, 216, 329, 330, 

346, 35° 
Iris. See Eye 
Iron, 216, 260, 270 
Islets of Langerhans, 271, 328. See 

Insulin, Pancreas 

Jaundice, hemolytic, 187 

Jaw, 205, 249, 257, 276, 295, 296, 304, 

309, 310, 325 
Jennings, H. S., 11, 43, 45 
Jimson weed. See Datura 
Joint, 306, 307, 310, 312, 313, 314. 

3i5» 34i 


Kidney, 209, 211, 222, 243, 248, 250, 
270, 282, 283, 284-86, 287, 331, 335' 
336, 339, 365; disease of, 352, 355, 
357, 366, 368 

Knee. See Limbs 

Labor (childbirth), 303, 315, 332, 341, 

Lamarck, 7 
Lamprey, 223 
Lancelet. See Amphioxus 
Landsteiner, Karl, 94 
Lange, Johannes, 216-17 
Larynx, 279, 280, 310, 321, 341 
Lathyrus. See Sweet pea 
Lead, 40 

Learning, 319, 321 
Lebistes, 106 
Lecithin, 60 

Lecomte du Noiiy, P., 362, 363 
Leeuwenhoek, 49 
Left-, right-handedness, 210 
Leg. See Limbs 
Lens. See Eye 
Lethal, 75-77, 79, 91-92, 137, 143. l68 < 

169, 185, 368; semi-, 75-77, 368 
Life, beginning of, 1-2; a continuum, 
7, 8; expectancy, 348, 349, 357, 358; 
length of, 367, 368; nature of, 6-7; 
span, 358-60; unity of, 20 
Ligament, 306, 313, 315, 340; of lens, 

291, 292, 293 
Light, 47, 136, 186, 197, 245, 289, 291, 

Lily, 137 

Limbs, 194, 202, 203, 205, 207, 209, 

257, 258, 259, 264, 303, 304-06, 311- 

16, 333, 337, 341. See Foot, Hand 

Linkage, 103-20; groups, 104-06, 116, 

160. See Sex, linkage 
Lipoid, 59, 360 

Lips. See Gastrula, Mouth, Vagina 
Liver, 209, 260, 261, 269-70, 271, 272, 

273, 325, 328 
Liverwort, 127, 146, 149; sperm (Pel- 
lia), 57. See Sphaerocarpus 
Lizard, 236, 289, 311 
Localization, of substances, 192-93, 

209, 224, 229 
Locomotion, 37, 58, 123, 229, 241. 

See Movement 
Locy, W. A., 13 
Loin, 304, 308, 327 
Louse, 350 
Lucretius, 48 
Lumbar. See Loin 
Lumbricus. See Earthworm 
Lung, 209, 222, 248, 257, 263, 264, 


265, 266-67, 268, 273, 274, 277-83 

Lygaeus, 147 
Lymantria, 156-57 

Lymph, gland, 260, 275; tissue, 261, 
272, 364; vessel, 272, 276 

Maize, 105, 117, 138, 139, 140-41, 184, 
186; barren-stalk, 145; crossing over 
in, 107-09; lazy, 107-09; nana, 198; 
starchy, sugary, 107-09; tassel-seed, 

Malaria, 349, 350 

Male, 113, 120, 121-22, 130-33, 133- 
38, 138-46, 147-57' *59> 162, 198- 
201, 254, 280, 285, 286, 334-41, 343- 
44> 357> 35 8 , 360 

Mammal, 59, 61, 125, 135, 199, 200, 
223, 261, 267, 281, 298, 301, 302, 
3°3> 304. 3 11 * 3!2, 315, 321, 322, 
324. 343- 344> 3 6 2; embryo, 242, 
2 57' 273, 295; mutants in, 75-76 

Mammary gland, 235, 257, 303, 346. 
See Breast 

Man, 129, 224, 234, 347; allelic series 
in, 93; chromosomes, 23, 149; chro- 
mosome number, 14, 15, 149; chro- 
mosome recombination in, 68-70; 
development, 155, 198-201, 223, 226- 
28, 229-30, 236-38, 242-43, 246-52, 
253. 255, 257-340; gametes in, 54- 
55; hearing in, 174-75; hereditary 
disease, 187, 196, 211, 214, 215, 368: 
life span, 358, 360, 362, 367; mu- 
tants, 73, 76-77, 78, 81-82, 88, 198, 
210, 310; races, 157, 173-74, 353; 
sex determination, 147-57; white, 
353. See Accident; Adolescence; 
Age, old; Ageing; Baby; Childhood; 
Disease; Eskimo; Maturity; Negro; 

Marrow. See Bone 

Mast, S. O., 41-42 

Mastoid, 296. See Bone 

Mating, 343-45, 347; types, 134-35. 
See Sex 

Maturity, 339, 340, 342, 347, 348, 359, 

Mealmoth. See Ephestia 

Mean, 177 

Measles, 351, 353, 354 

Medulla, of adrenals, 331; of brain, 
321, 323, 325-27; of gonads, 198, 

Megagamete, 54, 58, 62, 130, 132, 133, 

134. See Egg (ovum) 
Megaspore, 130, 132, 133 
Meiosis, 63, 64-70, 80-103, 104, 105, 

106, 108, 111, 118-20, 122-24, 125- 

29, 130, 131-33, 137-38, 139. 140-41. 
144, 145, 147, 148, 150, 153-55, 161. 
162, 171-73, 226, 336, 341, 342, 346; 
prophase, 1 1 1 

Melanin, 171 

Membrane, basilar, 299-301; brain, 
310; cell, 182, 228; egg, 58, 61; dif- 
ferentially permeable, 279; embry- 
onic, 246-52; fertilization, 62; hy- 
meneal, 337, 340; nuclear, 12, 21, 
22, 29, 182; peritoneal, 335; surface, 
33; tectorial, 299, 300; undulatory, 

Mendel, 13, 65, 80-81, 87, 99, 103, 119 

Meningitis, 350, 351 

Menopause, 216, 364 

Menstruation, 303, 342, 343, 345, 346 

Mesentery, 335 

Mesoderm, 242-46, 247, 248, 253-55, 
257, 260, 265, 271, 276, 281, 292, 

293, 3°3> 3°5> 3°6, 313' 33i, 335. 
336; segments, 255, 256, 282-85, 
304, 316, 326 

Metabolism, 39, 41, 44, 164, 191, 231, 
270, 283, 328, 330, 334, 338, 359-60, 

Metaphase. See Mitosis 

Methyl, group, 183, 184 

Microdissection, 36, 37 

Microgamete, 54, 55, 58, 62, 130, 132, 
133' 134- $ ee Sperm 

Microscope, 5; electron, 6 

Microspore, 130, 132, 133 

Midget, 178, 198, 333. See Dwarf 

Mineral, 216, 313, 364. See Calcium, 
Iron, Salt, etc. 

Minnow. See Fundulus 

Mirabilis jalapa, 88 -go, 92, 175 

Mirbel, 7 

Mite, 14 

Mitochondria, 31, 60 

Mitosis (cell division), 8-15, 18, 53, 
64, 66, 71, 122, 123, 124, 126, 131, 
132, 137, 167, 195, 221, 224-29, 233, 
261, 301, 341, 342, 362; anaphase, 
21, 22, 23, 24, 26, 33, 41, 129; 
block to, 53, 125, 128-29, 133; com- 
ponent processes, 25-31; duration 
of, 22-23; effect of temperature on, 
23; force, 35; metaphase, 21, 22, 23, 
24, 28, 66, 129; physical system, 31- 
37; prophase, 20-21, 22, 23, 24, 26, 
27, 28, 41, 63, 65, 66; rate of, 23, 40, 
182, 192; relation to reproduction, 
42-47; role of chemical substances 
in, 38-41; telophase, 21, 22, 23, 
24; types, 20-25; uniformity of, 19- 



Mohr, O. L., 76, 86, 201 

Mold, black, 146; bread (Mucor), 134; 

green, 351 
Mollusk, 129, 210 
Monaster, 34. See Spindle, half- 
Mongolian idiocy, 215 
Monkey, 227, 237, 259, 301, 316, 324, 

Monocotyledon, 62 

Monoecious, 141 

Montgomery, T. H., 65 

Morgan, Thomas Hunt, 73, 112 

Mosaicism, 181 

Mosquito, 15, 27, 349 

Moss, 124, 127, 144. See Funaria 

Moth, 156; gypsy (See Lymantria); 

meal- (See Ephestia); silkworm, 60, 

Mouse, 15, 82-85, 129, 168, 343, 346, 

352-53, 354; fieldmouse sperm, 57; 

short-ear, 208 
Mouth, 239, 240-41, 245, 253, 254, 

265, 268, 271, 275-77, 280, 296, 310, 

332; gum, 276; lips, 280, 322. See 

Jaw, Salivary gland, Tongue, Tooth 
Movement, 240, 242-46, 288, 326. See 

Mucor. See Mold 
Mucus, 236, 241, 244, 271, 279 
Mulatto, 171-73, 176 
Muller, H. J., 77, 112 
Mumps, 354 
Muscle, 210, 211, 243, 249, 259, 272, 

280-82, 292, 293, 294, 295, 302-07, 

312, 313, 315- 18 ' 325' 326, 328, 329> 

33 1 ' 332' 339, 364; cell, 241, 244; 

fiber, 271, 291, 304, 305, 317; tone, 

Mussel, 134 
Mutation, 71-80, 82, 92, 118, 129, 137, 

140, 143, 146, 147, 151, 156, 161, 

212, 222, 223, 311, 324; rate, 74, 

77-78. See Gene 

Nageli, 81 

Nails, 235, 301, 365 

Navel, 248, 249 

Neck, 255, 259, 262, 265, 275, 278, 
281, 282, 304, 307, 310, 325 

Negro, 170-74, 353; Bantu, 172; 
Pygmy, 157 

Nereis, 61 

Nerve, 210, 288, 302, 303, 305, 313, 
328, 329; auditory, 297, 298, 300, 
325; cell, 229, 240, 241, 245, 289, 
316-20, 318, 322, 327, 331; cranial, 
325; (dendrite), 317; fiber, 276, 299, 
300, 317, 318, 320, 322, 324, 325, 

326, 327; impulse, 317, 318, 319; 
olfactory, 325; optic, 289, 292, 324, 

Nervous system, 192-93, 235, 242, 246, 
254, 256, 259, 3 l6 -27> 3 6 5; auto- 
nomic, 302, 326-27; diseases of, 366; 
parasympathetic, 327; sympathetic, 
326-27, 331 

Neural crest, 326 

Neural groove, 242, 253, 254, 255, 256 

Neural tube, 192-93, 194, 242, 255, 
256, 257, 283, 316, 320, 326 

Newman, H. H., Freeman, and Hol- 
zinger, 218 

Nondisjunction, 150-53, 156, 180 

Nordenskiold, E., 13 

Normality, 175, 177-79 

Normal frequency, curve, 177; distri- 
bution, 177-79 

Nose, 194, 258, 259, 277, 279, 280, 

288, 310. See Smell 
Notochord, 255, 256, 257, 269, 283, 

287, 306, 307 

Nucleolus, 27, 28 

Nucleoprotein, 60 

Nucleus, 12, 14, 15, 20, 21, 28, 29, 31, 
32, 34, 37- 4o, 55> 57-63' 67' 122, 
126, 130, 132, 133, 191, 225, 226, 
228, 244, 261, 304; macro-, 361 

Nutrition, 205, 211, 215, 216, 231, 
240, 246-52, 260, 268-77, 351. See 
Diet, Food 

Oat, 197 

Obelia, 40 

Oenothera, 106 

Olfactory. See Nose, Nerve 

Onion. See Allium cepa 

Oogenesis, 130 

Optic. See Eye, Nerve 

Organizer, 192-95, 199, 201, 209, 242. 

289, 328 
Osmosis, 263 
Otolith. See Ear 
Outbreeding. See Crossbreeding 
Ovary, 50, 182, 191, 198-201, 246, 334- 

36, 338-43. See Gonad; Reproduc- 
tion, organs of 

Oviduct, 155, 339, 342, 344' 346 

Ovulation, 227, 342, 343, 345' 34 6 

Ovule, 58, 59, 132 

Ovum. See Egg 

Oxidation, 41, 164, 166, 270; rate of, 

39' 4° 
Oxygen, 31, 39, 41, 191, 229, 238, 248, 

250, 251, 260, 263, 265, 266, 268, 

277, 278, 279 
Oyster, 139 


Pain, 288, 322 

Palate, 277, 310; cleft, 76, 310 

Pancreas, 209, 269, 271-73, 274, 325, 

328, 334 
Paracelsus, 48 

Paramecium, 42, 43, 67, 122, 135, 229 
Parasite, 2, 54, 60, 124, 136, 196, 254, 

Parathyroid gland, 274, 275, 328, 329, 


Parentage, 95-96 

Parthenogenesis, 129 

Pasteur, 3-4, 7, 13, 50-52, 60, 234, 349, 
351; pasteurization, 4 

Pattern, body, 190 (See Form); cul- 
ture, 233; developmental, 222 (See 
Homology); molecular, 190. See 

Pea, 81, 122, 137, 143; independent 
assortment in, 99 

Pearl, Raymond, 367, 368 

Pearson, Karl, 367 

Peattie, D. C, 234 

Pebrine, 60 

Pelargonidin, 183 

Pellagra, 211, 351, 366 

Pelvis, 261, 308, 311, 315, 341; of 
kidney, 285 

Penicillin, 351 

Penis, 246, 337, 339, 344; glans of, 

337' 33 8 > 344 
Pepsin, 272 

Perception, 287-301. See Sense organ 
Peristalsis, 271, 303 
Peritonitis, 350 
Personality, 218, 329-30 
pH, 10, 36, 184, 186. See Hydrogen 

Phallus, 337, 338-40 
Pharynx, 245, 273-75, 278, 279, 280, 

325; pouch, 257, 265, 269, 273, 274, 

277» 294, 328, 330 
Phenotype, 88, 92, 96, 97, 100, 108, 

109, 118, 143, 144, 170, 176, 185-87, 

189, 196, 212-14 
Phenotypic ratio, 85, 89, 90, 98, 100, 

101-02, 109, 170, 176, 177 
Phenyl-thio-carbamide, 288 
Phospholipin, 165 
Phosphorus, 59-60, 216 
Photosynthesis, 39, 45, 60 
Pigment, 60, 182, 225, 291; bile, 270; 

carotenoid, 184-85; co-, 183; eye, 

169-70, 185; flower, 183-84, 186; 

skin, 170-74. See Albinism, Antho- 

cyanin, Anthoxanthin, Melanin 
Pineal body, 289, 323 
Pitch, 280, 300. See Hearing 

Pituitary gland, 194, 201, 209, 269, 

277- 323> 332-34' 34o, 343' 345' 34^ 

Placenta, 247, 248, 252, 257, 260, 262, 
263, 264, 267, 269, 270, 342, 345, 355 

Planaria, 55, 223, 244, 359 

Plant, alternation of generations in, 
126-28, 129, 181; cell division, 12, 
13, 24-25; flowering (seed), 58, 59, 
62, 88, 121-22, 124, 127, 130, 137; 
gametes, 53-64, 130-33; hormones, 
197-98; sex in, 121-22, 135-38, 140- 
41; unicellular, 122, 229; vegetative 
reproduction, 43. See Alga, Fern. 
Liverwort, Maize, Moss 

Plasma. See Blood 

Plastid, 25, 31, 60, 131, 183, 188 

Pleodorina, 45, 46 

Pneumonia, 350, 351, 352, 355, 357, 

Poikilothermy, 361 

Polar body, 10, 132, 133, 226, 227, 

Polarity, 35, 191-93, 194 

Pole, animal and vegetal, 191, 22^, 
226, 234, 235, 236, 239. See Spindle 

Pollen grain, shape, 104. See Micro- 

Pollen tube, 57, 62, 132 

Pollution, water and milk, 350 

Polydactyly, 76, 187 

Polyp. See Hydra, Hydroid 

Polysaccharide, 354 

Pons, 323, 325, 326 

Pore, genital, 244, 246; primitive, 192, 
193, 242, 243, 253, 254, 255 

Position effect, 79, 161 

Potassium, 216, 332; cyanide, 28 

Precedence (epistasis), 169, 170 

Precursor substances, 167, 184, 185, 
186, 192, 196, 216 

Preformation, 49-50 

Pregnancy, 330, 343, 344, 345-47 

Primate, 301, 347. See Ape, Man, 

Primitive streak, 242-43, 253, 254, 
256; groove, 243, 254; pit, 254 

Probability, of coincidence, 101; of 
death, 365-66; of gene recombina- 
tion, 116; of inheritance, 177. See 

Proboscis, 244, 245 

Progestin, 342, 345, 346 

Prolactin, 346 

Prophase. See Meiosis, Mitosis 

Prostate gland, 341, 344, 364 

Protection, 240, 246-52, 306 

Protein, 5-6, 42-43, 59-60, 93, 164. 
165, 180, 196, 251, 260, 270, 272, 


285, 329, 354, 360; fibrous, 29; hu- 
man, 166, 167. See Globulin, Nu- 

Pro tenor, 149 

Prothrombin, 261 

Protoplasm, 5, 9, 10, 12, 13, 36, 42, 
54, 63, 67, 126, 131, 164, 165, 193, 
228, 229, 360, 361; renewal of, 44; 
viscosity of, 32, 35 

Protozoa, 32, 126, 144, 223, 361. See 
Aggregata eberthi, Ameba, Chilo- 
monas, Gregarine, Sporozoa 

Pseudopod, 123, 241 

Pteridophyte. See Fern 

Ptolemies, 143 

Ptyalin, 276 

Puberty, 330, 335, 336, 340-43. 3 6 4 

Pupil. See Eye 

Pure line, 43-44 

Putrefaction, 3-4 

Pyronema, 67 

Quadruped, 308, 312 
Quinine, 28, 350 
Quintuplets, 219, 227 

Rabbit, 41; albino, 88, 92-93; chin- 
chilla, 93; Himalayan, 92-93; mul- 
tiple alleles in, 92-93, 164, 168, 345, 

Rabies, 351 
Race, 96-97, 156, 157; intermixture, 

172-73; prejudice, 174 
Rat, 15, 41, 168, 215, 350, 353, 358, 


Ray (elasmobranch), 257 

Reaction speed, 356 

Recessiveness, 82, 83, 87, 88, 90, 92- 
93, 100-02, 107, 109, 143, 158, 168, 
170, 174, 175, 184, 185, 196, 246. 
See Allele 

Recombination, 147, 156, 162. See 
Allele, Chromosome, Gene 

Redi, 49 

Reduction, 39, 40, 129. See Meiosis 

Reflex, 280, 281, 319, 322, 324, 325, 
326, 327; arc, 318 

Reproduction, 7, 9, 10, 12, 13, 122-24; 
asexual, 42-47, 128, 189, 241; in 
flatworms, 246; in Hydra, 240, 241; 
organs of, 121, 139, 198-201, 243, 
246, 250, 286, 335-43. 364 ( See Duct, 
sexual; Gonad, Ovary, Testis); re- 
productive (germ) cell, 8, 11, 53-71, 
103, 125, 128, 129, 131, 133, 139. 
149, 150, 189, 198, 200, 231, 251 
(See Sex, cell); sexual, 53-71, 80- 
120, 124-33, 241. 334-47 


Reptile, 223, 236, 238, 248, 250, 257, 
261, 267, 277, 282, 295, 296, 31 1, 
320, 344 

Resonance, 280 

Respiration, 41, 231, 240, 246-52, 257, 
260, 265, 277-82, 326; respiratory 
disease, 366. See Cold, Influenza, 
Pneumonia, Tuberculosis 

Response, 197, 240, 260, 301-16; max- 
imum, 186-88 

Retina. See Eye 

Rhizopod, 32, 58. See Ameba 

Rhodnius, 195 

Rib. See Bone 

Roller, Duane, 19 

Rose, 137 

Roundworm, 248, 253-54, 256. See 

Roux, 14 

Rudiment. See Bud 

Sacculus, 294, 297, 298, 299. See Ear 

Sacrum. See Bone 

Salamander, mitosis in, 20-22; Sala- 
mandra maculosa, 22, 23, 182, 192, 
209, 242, 257, 267; sperm, 58 

Salivary gland, chromosome, 17, 18, 
79, 118, 168; human, 276, 325 

Salt, 25, 39, 59, 125, 164, 260, 270, 
302, 307, 330 

Salvarsan, 350 

Scales, 235 

Scapula. See Bone 

Scarlet fever, 351, 353 

Scheinfeld, A., 77 

Schleiden, 7 

Schrader, F., 35 

Schwann, 7-8 

Sciara, 30, 34 

Scrotum, 337, 340 

Scurvy, 351 

Sears, P. B., 163 

Season, 138, 140, 241, 303 

Sea urchin, 35, 60, 129, 134 

Secretin, 272, 328 

Secretion. See Gland, Hormone 

Segment, mesodermal, 255, 256, 282- 
85, 304, 307, 316, 326 

Segregation, 147, 162. See Allele, 

Seifriz, W., 38 

Selection, artificial, 43, 44, 214; natu- 
ral, 13, 143, 154, 161, 222 

Semen, 341, 344 

Seminal vesicles, 341 

Senescence. See Ageing 

Sensation, 240 

Sense organ, 235, 243, 287ff., 316. See 



Ear, Eye, Nose, Nerve, Tongue 
Sensory cell, 240, 241, 245, 288, 297, 

299, 300 
Serum (treatment, immunization), 

351. See Blood, serum 
Sex, 18, 42, 116, 215; biopotentiality, 
134-38, 153, 162; cell, 65, 136, 201, 
286, 335, 336, 341 (See Reproduc- 
tion, cell); definition of, 53, 123, 

134, 135; determination, 120, 129, 
136, 139. 140-41. 144-46, 147-57' 161, 
162, 334; differentiation, 133-37, 
198-201, 259, 330, 332, 334-43; ge- 
netic basis of, 121-62; heteroga- 
metic, 156, 157; inter-, 135, 153, 
156, 199; isolation of, 121, 122, 135, 
138-47, 157, 162, 254; linkage, 140, 
157-62, 181; mechanism of, 121-24; 
multiplicity of, 135, 146, 147; organs, 
136, 140, 200-01, 209, 241, 284, 287, 
335-44; ratio, 140, 154-55; reversal, 

135, 139, 162, 199, 200, 338; sub- 
stance, 134; urge, 343. See Chro- 
mosome, sex; Female; Gene, sex; 

Shark, 257, 336 

Sheep, Ancon, 72 

Shepherd's purse (Bursa), 174 

Shoulder, 264, 306, 311, 312, 313, 341 

Silkworm. See Moth 

Simms, Henry S., 365, 366 

Sinus, 261; of head, 280; urogenital, 

269; venosus (See Vein, trunk) 
Skate, sperm (Raja), 57 
Skeleton, 305, 306-16, 329, 330, 333 
Skin, 235, 243, 288, 290, 301-03, 310, 

316, 33°. 33i> 333' 35°> 3 6 4> 3 66 ; 
pigmentation, 77, 170-74, 175. See 

Skull, 204, 208, 293, 296, 297, 304, 
307, 309 

Smallpox, 349, 351, 353 

Smell, 320, 322, 324, 325. See Nose 

Smith, H. W., 278 

Snail, 34, 210. See Crepidula 

Society, human, 232-34, 324, 370 

Sodium, 216, 332 

Soil, 136 

Sol, 9, 36 

Solar plexus, 327, 331 

Solution, hypertonic, 34, 35, 125; hy- 
potonic, 35 

Soma, 11, 78, 189-90 

Specialization, 190, 224, 230-32, 370. 
See Cell, differentiation 

Speech, 280, 322 

Spemann, H., 201 

Sperm (spermatozoon), 5, 10, 34, 49, 

60-65, 68, 82, 84, 98, 99, 103, 121, 
125, 130, 132, 134, 146, 147-5°' 152- 
56, 191, 225, 227, 241, 246, 285, 334, 
335-37» 344» 355^ animal, 55, 57; 
human, 54-55, 56, 339, 341; mid- 
piece, 55, 61; plant, 55-58; types 
of, 57. See Gamete 

Spermatogenesis, 130 

Spermatophyte. See Plant, flowering 

Sphaerocarpus, 145 

Sphincter, 272 

Spinal column. See Backbone 

Spinal cord, 192, 242, 255, 269, 287, 
307, 308, 316-20, 321, 322, 325, 326 

Spindle, 12, 13, 27, 62, 63, 65, 68; at- 
tachment (See Centromere); hipo- 
larity, 34-35; central (accessory), 21. 
22, 23, 29, 33; fiber, 21, 22, 29; for- 
mation, 25, 28-30, 33-35, 36; half-, 
30, 34; orientation of, 131-32, 226; 
true, 23-24, 29, 34 

Spirogyra, 125, 126, 127 

Spleen, 209, 260, 261 

Sponge, 239 

Spontaneous generation, 2-7, 48-52 

Spore, 4, 45, 47, 53, 124, 125, 127, 128, 
129, 130, 133, 137, 359 

Sporophyte, 127, 128, 145 

Sporozoa, 58, 126 

Squash, 138, 208 

Stanley, W. M., 5 

Starch, 276 

Stature, 178, 180, 216, 259, 332-34, 

Stenobothrus, 30 

Sterility, 150, 151, 153, 156, 201, 205 

Stern, Curt, 109 

Sternum. See Bone, breastbone 

Sterol, 59, 165, 193, 339 

Stirrup. See Bone 

Stomach, 209, 210, 248, 269, 270, 272. 
273' 274, 303, 325, 328 

Strasburger, 12, 13, 14, 103 

Streptococcic sore throat, 350 

Sturtevant, A. H., 112; and G. W. 
Beadle, 181, 185 

Suffocation, 279, 280 

Sugar, 39, 183, 190, 238, 269, 271, 272, 
288, 331, 354 

Sulfur, 39, 40, 216 

Sulfa drug, 297, 350, 351 

Sulfhydryl, 39, 40 

Surface tension, 32, 37 

Sutton, W. S., 104-05 

Swammerdam, 49 

Sweet pea (Lathyrus), 105, 175 

Symmetry, bilateral, 191, 209, 243, 
246; axes of, 191-93, 201, 208, 242; 



planes of, 191, 201; radial, 241. 
See Asymmetry 

Sympathin, 327, 331 

Synapse, 318-19 

Synapsis, 65-67, 149 

Synchronization, 26, 33, 67, 128 

Syngamy, 54, 62-64, 67, 71, 80-103, 
108, 118, 120, 123-28, 131, 133, 134, 
i37» 139' 140-41. 144-45. 147-50, 152, 
154, 157, 161, 162, 171-73. See Fer- 

Synthesis, 6, 60, 164-67, 169, 170, 175, 
184, 197, 260, 331; dehydration, 

Syphilis, 350, 353 

Tail, 192, 242, 255, 258, 262, 271, 286, 
304, 306, 308, 337, 338; of sperm, 
55. 58, 61 

Tapeworm, 350 

Taste, 245, 288, 322 

Teleology, 221-22 

Telophase. See Mitosis 

Temperament, 218 

Temperature, coefficient, 41; effect of, 
31, 36, 41, 116, 125, 186, 189, 212- 

14, 303. 323' 329, 3 6 i 
Tendon, 210, 305, 315 
Tentacle, 239, 241 
Testis, 198-201, 246, 285, 334-36, 338- 

41; tubules, 335, 339, 341. See 

Testosterone, 338 
Tetrad, 65 
Tetraploid(y), 27 
Thalamus, 321, 322-25, 327, 332 
Theelin, 338, 342, 343, 345, 346 
Thigh. See Limbs 
Thompson, D'Arcy, 32, 206 
Threshold, 186-88, 193, 200 
Throat, 304. See Pharynx 
Thumb, 313, 315, 316 
Thymus, 260, 274, 275, 330, 364 
Thyroid gland, 211, 269, 273, 274, 

328, 329-30, 334, 345 
Thyroxin, 209, 329, 330, 334 
Timbre, 301 

Time, physiological, 364 
Tissue, 221. See Connective tissue; 

Lymph, tissue 
Tissue-culture, 37, 44, 304, 362 
Toad, 58, 257, 267; sperm, 57 
Tobacco, mutant, 72 
Toe. See Digit 

Tone, muscle, 288. See Hearing 
Tongue, 269, 275, 279, 280, 288, 310, 

325. See Taste 
Tonsil, 275, 364 

Tooth, 204, 209, 276-77, 280, 329, 359, 
364; cement, 276; dentine, 276; 
enamel, 235, 276; pulp, 276 

Tortoise, 358-59 

Touch, sense of, 288 

Trachea, 269, 274, 278, 279, 280, 325, 


Trait, physical, 218, 219; relation to 
genes, 168-80, 185, 214; sex-linked, 
158-60, 181, 196. See Allele, blend- 
ing, dominant, recessive; Character; 
Environment, and heredity; Hered- 
ity, and environment 

Translocation, 105, 106, 109, 147 

Transplantation, 181-82, 192-93, 194, 
196, 209, 333 

Trichina, 350 

Triploid(y), 152; endosperm, 62, 133, 

Trunk, 193, 205, 306, 308, 333. See 

Trypanosome, 58 

Tschermak, 81 

Tuberculosis, 338, 349, 351, 353, 357, 

Tubule. See Excretion, Testis 

Turpin, 7 

Twins, 199, 215-19, 227, 288, 347, 353, 
369; Schweizer, 217-18 

Tympanic cavity, 294. See Ear 

Tyndall, 3 

Typhoid fever, 4, 349 

Typhus fever, 349, 350, 351 

Umbilical cord, 248, 249, 252, 262, 
269; arteries, 262; vein, 262, 269 

Urea, 238, 270 

Ureter, 285, 286, 287 

Urethra, 286, 287, 336, 337, 338, 339, 

Urine, 251, 285, 286, 303, 332, 345 

Urogenital ridge, 284, 335 

Use, effects of, 210-11, 282, 305, 356 

Uterus, 59, 60, 136, 155, 200, 215, 221, 
236, 238, 246, 251, 257, 303, 315, 
332, 339, 342, 344, 345, 346; mucosa 
of, 237, 238, 246, 252, 342, 345 

Utriculus, 294, 297, 298, 299 

Vacuole, contractile, 32, 123; sap, 229 

Vagina, 60, 293, 315, 337, 339, 340, 
344; major lips, 337, 340; minor 
lips, 337' 340 

Van Beneden, 13 

Van Helmont, 48 

Variation, 42, 43, 352; effect of link- 
age and crossing over on, 103-20, 
162; in environment, 187; environ- 

3 86 


mentally caused, 53, 164, 178, 180; 
hereditary, 20, 53, 71-80, 80-103, 
103-20, 121-24, 161-62, 178, 359; 
normal, 177-78, 186, 188, 333; quan- 
titative, 175-80. See Chromosome, 
assortment; Gene, Heredity, Re- 

Variegation, 181 

Vein, 250, 256, 262, 263, 265, 270, 272, 
284. 335; pulmonary, 268; trunk 
(sinus venosus), 266, 268; umbilical, 
262, 269 

Ventricle, 266, 267, 268 

Vergil, 48 

Vertebra, 307, 308, 310, 311. See 

Vertebrate, 74, 82, 129, 160, 181, 199, 
223, 248, 273, 281, 311, 315, 320, 
324. See Amphibian, Bird, Fish, 
Mammal, Reptile 

Vestigial organs, 224, 312 

Viability, 74-77, 169, 222 

Villus, 238, 247, 252, 272 

Virchow, 7-8 

Virus, 5-7, 43, 60; infantile paralysis, 
5; influenza A, 6; rabies, 351; to- 
bacco mosaic, 5-6 

Viscosity, 9, 35-37 

Vitamin, 6, 211, 219, 346; A, 184, 216; 
K, 216, 261. See Acid, nicotinic 

Vitellin, 60 

Vision, 320, 322, 324, 325. See Eye 

Vocal cord, 280, 310, 341 

Voice, 280, 341 

Volvox, 45, 46, 124-26, 228, 230-31 

Von Baer, 50 

Wasp, 129. See Habrobracon 
Wastes, 238, 245, 250, 251, 260, 263, 
270, 282-87, 361. See Excretion 

Water, 40, 59, 61, 164-66, 230, 257, 
263, 265, 271, 278, 302, 344, 350, 
360; sea, 260. See Synthesis, dehy- 

Weight, 175, 178, 179, 216, 259, 360 

Weismann, August, 11 

Wells, H. G., Huxley, Wells, 90, 155 

Will, free, 232 

Willow, 122 

Wilson, E. B., 9, 35 

Wilson's disease, 76 

Windpipe. See Trachea 

Wolff, 49 

Womb. See Uterus 

Worm, 129, 303; segmented, 248, 284. 
See Bonellia, Earthworm, Flat- 
worm, Nereis, Roundworm 

Wound, healing (cicatrization), 363- 
64; infection, 350 

Wrist. See Limbs 

X-chromosome, 146-56, 158-61, 334; 

attached-X, 16-17 
X-ray, 5, (vj$(Tj7) 10 £> 10 ^> 1J 6> 211, 

275> 336 

Y-chromosome, 146-51, 154-56, 158-61, 

Yeast, 43 

Yellow fever, 349, 353 
Yolk, 58, 62, 191, 225, 226, 229, 234, 

236, 249, 251; composition of, 59 
Yolk sack, 236, 237, 247, 249, 252, 

253, 254, 260, 262, 268, 269, 271 

Zea. See Maize 

Zygote, 11, 54, 60, 64, 83-84, 103, 122, 
124, 125, 126, 131, 132, 133, 137, 
144, 148, 189, 210, 215, 224, 227, 
236, 342, 345 


Genes and the man, sci 

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